Immune system plasticity during aging: Immunomodulatory capacity of oestrogens

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Immune system plasticity during aging: Immunomodulatory capacity of oestrogens (en)
Пластичност имунског система током старења: имуномодулаторни потенцијал естрогена (sr)
Plastičnost imunskog sistema tokom starenja: imunomodulatorni potencijal estrogena (sr_RS)
Authors

Publications

Fenotipske karakteristike peritonealnih makrofaga dva soja pacova tokom razvoja inflamatornog odgovora: značaj predstavnika crevne mikrobiote

Blagojević, Veljko

(Универзитет у Београду, Биолошки факултет, 2022)

TY  - THES
AU  - Blagojević, Veljko
PY  - 2022
UR  - https://eteze.bg.ac.rs/application/showtheses?thesesId=8991
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:28087/bdef:Content/download
UR  - https://nardus.mpn.gov.rs/handle/123456789/21207
UR  - http://intor.torlakinstitut.com/handle/123456789/677
AB  - Predmet istraživanja ove doktorske disertacije je ispitivanje promena u fenotipu i aktivnosti makrofagaperitonealne šupljine Albino Oxford (AO) i Dark Agouti (DA) pacova tokom razvoja inflamatornogodgovora koji je indukovan delovanjem bakterija mikrobiote creva direktno, intraperitonealnom (i.p.)primenom, ili indirektno, tokom razvoja kolitisa, kao i ispitivanje modulacije ovih promena primenomprobiotske bakterije Lactobacillus rhamnosus (L. rhamnosus).Rezultati su pokazali da i.p. primena umrtvljenih E. coli ili Enterococcus spp. dovodi do izraženijeinflamatorne polarizacije makrofaga peritonealne šupljine DA pacova u odnosu na AO soj, dok i.p.primena L. rhamnosus ima veći potencijal da spreči funkcionalne promene do kojih dovodi in vitrostimulacija komensalnim bakterijama u makrofagima pacova AO soja. Tokom razvoja kolitisamakrofagi DA pacova produkuju više IL-6 u odnosu na AO soj, a značajno manja smrtnost AO pacovaje praćena intenzivnijom produkcijom IL-10 u makrofagima u odgovoru na dodatnu stimulacijukomensalnim bakterijama in vitro i višim nivoom antitela klase IgA specifičnih za E. coli u serumu. Ranipostnatalni oralni tretman bakterijom L. rhamnosus u DA pacovima povećava raznovrsnostBifidobacterium vrsta u fecesu, a nakon indukcije kolitisa u adultnom dobu smanjuje stepen ulceracijekolona, povećava zastupljenost rezidentnih makrofaga peritonealne šupljine i suprimira povećanjaprodukcije NO i IL-10 stimulisana komensalnim bakterijama in vitro.Nalazi ukazuju na značaj genetski determinisane predispozicije ka određenom obrascu aktivacijemakrofaga za promene u fenotipu i aktivnosti tokom razvoja inflamatornog odgovora koji je indukovandelovanjem bakterija mikrobiote creva, kao i za modulaciju ovih promena primenom probiotskebakterije L. rhamnosus.
AB  - The subject of this doctoral dissertation is the study of changes in the phenotype and activity ofperitoneal cavity macrophages from Albino Oxford (AO) and Dark Agouti (DA) rats during thedevelopment of inflammatory response induced by intestinal microbiota directly, intraperitoneally (i.p.),or indirectly, through development of colitis, as well as study of the modulation of these changes usingthe probiotic bacterium Lactobacillus rhamnosus (L. rhamnosus).I.p. application of killed E. coli or Enterococcus spp. leads to a more pronounced inflammatorypolarization of the peritoneal cavity macrophages from DA rats compared the AO strain, while i.p.application of L. rhamnosus has a greater potential to prevent functional changes caused by in vitrostimulation with commensal bacteria in AO rat macrophages. During the development of colitis, DArat macrophages produce more IL-6 than the AO strain, and significantly lower AO rat mortality wasaccompanied by more intense IL-10 production in macrophages in response to additional stimulationwith commensal bacteria in vitro and higher levels of IgA-class antibodies specific to E. coli in the serum.Early postnatal oral treatment with L. rhamnosus in DA rats increased the diversity of Bifidobacteriumspecies in feces, and after induction of colitis in adulthood reduced the degree of colonic ulceration,increased the presence of resident peritoneal cavity macrophages and suppressed the increasedproduction of NO and IL-10 stimulated by commensal bacteria .The findings indicate the importance of genetically determined predisposition to a certain pattern ofmacrophage activation for changes in phenotype and activity during the development of inflammatoryresponse induced by intestinal microbiota, as well as for modulation of these changes using probioticbacterium L. rhamnosus.
PB  - Универзитет у Београду, Биолошки факултет
T2  - Универзитет у Београду
T1  - Fenotipske karakteristike peritonealnih makrofaga dva soja pacova tokom razvoja inflamatornog odgovora: značaj predstavnika crevne mikrobiote
UR  - https://hdl.handle.net/21.15107/rcub_nardus_21207
ER  - 
@phdthesis{
author = "Blagojević, Veljko",
year = "2022",
abstract = "Predmet istraživanja ove doktorske disertacije je ispitivanje promena u fenotipu i aktivnosti makrofagaperitonealne šupljine Albino Oxford (AO) i Dark Agouti (DA) pacova tokom razvoja inflamatornogodgovora koji je indukovan delovanjem bakterija mikrobiote creva direktno, intraperitonealnom (i.p.)primenom, ili indirektno, tokom razvoja kolitisa, kao i ispitivanje modulacije ovih promena primenomprobiotske bakterije Lactobacillus rhamnosus (L. rhamnosus).Rezultati su pokazali da i.p. primena umrtvljenih E. coli ili Enterococcus spp. dovodi do izraženijeinflamatorne polarizacije makrofaga peritonealne šupljine DA pacova u odnosu na AO soj, dok i.p.primena L. rhamnosus ima veći potencijal da spreči funkcionalne promene do kojih dovodi in vitrostimulacija komensalnim bakterijama u makrofagima pacova AO soja. Tokom razvoja kolitisamakrofagi DA pacova produkuju više IL-6 u odnosu na AO soj, a značajno manja smrtnost AO pacovaje praćena intenzivnijom produkcijom IL-10 u makrofagima u odgovoru na dodatnu stimulacijukomensalnim bakterijama in vitro i višim nivoom antitela klase IgA specifičnih za E. coli u serumu. Ranipostnatalni oralni tretman bakterijom L. rhamnosus u DA pacovima povećava raznovrsnostBifidobacterium vrsta u fecesu, a nakon indukcije kolitisa u adultnom dobu smanjuje stepen ulceracijekolona, povećava zastupljenost rezidentnih makrofaga peritonealne šupljine i suprimira povećanjaprodukcije NO i IL-10 stimulisana komensalnim bakterijama in vitro.Nalazi ukazuju na značaj genetski determinisane predispozicije ka određenom obrascu aktivacijemakrofaga za promene u fenotipu i aktivnosti tokom razvoja inflamatornog odgovora koji je indukovandelovanjem bakterija mikrobiote creva, kao i za modulaciju ovih promena primenom probiotskebakterije L. rhamnosus., The subject of this doctoral dissertation is the study of changes in the phenotype and activity ofperitoneal cavity macrophages from Albino Oxford (AO) and Dark Agouti (DA) rats during thedevelopment of inflammatory response induced by intestinal microbiota directly, intraperitoneally (i.p.),or indirectly, through development of colitis, as well as study of the modulation of these changes usingthe probiotic bacterium Lactobacillus rhamnosus (L. rhamnosus).I.p. application of killed E. coli or Enterococcus spp. leads to a more pronounced inflammatorypolarization of the peritoneal cavity macrophages from DA rats compared the AO strain, while i.p.application of L. rhamnosus has a greater potential to prevent functional changes caused by in vitrostimulation with commensal bacteria in AO rat macrophages. During the development of colitis, DArat macrophages produce more IL-6 than the AO strain, and significantly lower AO rat mortality wasaccompanied by more intense IL-10 production in macrophages in response to additional stimulationwith commensal bacteria in vitro and higher levels of IgA-class antibodies specific to E. coli in the serum.Early postnatal oral treatment with L. rhamnosus in DA rats increased the diversity of Bifidobacteriumspecies in feces, and after induction of colitis in adulthood reduced the degree of colonic ulceration,increased the presence of resident peritoneal cavity macrophages and suppressed the increasedproduction of NO and IL-10 stimulated by commensal bacteria .The findings indicate the importance of genetically determined predisposition to a certain pattern ofmacrophage activation for changes in phenotype and activity during the development of inflammatoryresponse induced by intestinal microbiota, as well as for modulation of these changes using probioticbacterium L. rhamnosus.",
publisher = "Универзитет у Београду, Биолошки факултет",
journal = "Универзитет у Београду",
title = "Fenotipske karakteristike peritonealnih makrofaga dva soja pacova tokom razvoja inflamatornog odgovora: značaj predstavnika crevne mikrobiote",
url = "https://hdl.handle.net/21.15107/rcub_nardus_21207"
}
Blagojević, V.. (2022). Fenotipske karakteristike peritonealnih makrofaga dva soja pacova tokom razvoja inflamatornog odgovora: značaj predstavnika crevne mikrobiote. in Универзитет у Београду
Универзитет у Београду, Биолошки факултет..
https://hdl.handle.net/21.15107/rcub_nardus_21207
Blagojević V. Fenotipske karakteristike peritonealnih makrofaga dva soja pacova tokom razvoja inflamatornog odgovora: značaj predstavnika crevne mikrobiote. in Универзитет у Београду. 2022;.
https://hdl.handle.net/21.15107/rcub_nardus_21207 .
Blagojević, Veljko, "Fenotipske karakteristike peritonealnih makrofaga dva soja pacova tokom razvoja inflamatornog odgovora: značaj predstavnika crevne mikrobiote" in Универзитет у Београду (2022),
https://hdl.handle.net/21.15107/rcub_nardus_21207 .

Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju

Ćuruvija, Ivana D.

(Univerzitet u Beogradu, Farmaceutski fakultet, 2021)

TY  - THES
AU  - Ćuruvija, Ivana D.
PY  - 2021
UR  - http://intor.torlakinstitut.com/handle/123456789/619
AB  - Starenje se povezuje sa razvojem sistemskog, sterilnog hroničnog zapaljenja (engl. „inflammaging”). Malo je podataka o uticaju genetskih faktora i pola na sposobnost makrofaga (Mϕ), kao ključnih ćelija urođenog imunskog odgovora, da tokom starenja “kontrolišu” rezoluciju akutnog zapaljenja i time razvoj hroničnog zapaljenja. Ciljevi ove disertacije su bili da se ispita 1) uticaj rane faze reproduktivnog starenja na fenotipske osobine (ekspresija markera povezanih sa aktivacijom i poreklom/funkcijom) i funkcijska svojstva (fagocitoza, sinteza inflamatornih medijatora) Mϕ “mirne” i inflamirane (delovanjem tioglikolata) peritonealne duplje ženki Albino Oxford (AO) pacova, 2) značaj genetskih faktora za reproduktivnim starenjem uslovljene promene peritonealnih Mϕ od značaja za uspešnu rezoluciju akutnog zapaljenja i 3) uloga polnih steroida u nastanku ovih promena uporednom analizom promena kod mužjaka i ženki AO pacova, njihovom analizom kod ženki AO pacova kojima su na kraju reproduktivnog perioda uklonjeni jajnici i ispitivanjem delovanja estradiola na Mϕ mladih i sredovečnih ženki AO pacova in vitro. Rezultati su pokazali da: 1) se sposobnost Mϕ ženki AO pacova da “kontrolišu” rezoluciju akutnog zapaljenja menja već tokom rane faze reproduktivnog starenja, kao i da su ove promene sojno specifične (Mϕ sredovečnih ženki AO pacova koje “uspešnije” stare od ženki Dark Agouti pacova pokazuju svojstva koja se mogu povezati sa boljom “kontrolom” inflamacije); 2) su ove promene polno specifične (Mϕ sredovečnih ženki imaju svojstva koja ukazuju na veći kapacitet da “kontrolišu” inflamaciju od Mϕ mužjaka istog uzrasta) i 3) u nastanku promena relevantnih za sposobnost Mϕ ženki AO pacova da “kontrolišu” akutnu inflamaciju važnu ulogu imaju promene u delovanju i estradiola i progesterona. Dodatno, ispitavanja in vitro su ukazala da su za uzrasno zavisne promene u sposobnosti Mϕ da “kontrolišu” inflamaciju pored promene u koncentraciji estradiola važne i one u samim Mϕ, koje menjaju njihov odgovor na delovanje estradiola.
AB  - Aging is associated with the development of systemic, sterile chronic inflammation ("inflammaging"). Little is known about the influence of genetic factors and sex on the ability of macrophages (Mϕ), as key innate immune cells, to "control" the resolution of acute inflammation and thus the development of chronic inflammation during aging. The objectives of this dissertation were to examine 1) the influence of the early phase of reproductive aging on phenotypic characteristics (expression of markers associated with activation and origin/function) and functional characteristics (phagocytosis, synthesis of inflammatory mediators) of Mϕ isolated from “naive” and inflamed (thioglycollate-induced) peritoneal cavity of females Albino Oxford (AO) rats; 2) the significance of genetic factors for reproductive aging-related changes of peritoneal Mϕ, especially those important for successful resolution of acute inflammation and 3) the role of sex steroids in the occurrence of these changes by comparative analysis in males and females of AO rats, their analysis in female AO rats whose ovaries were removed at the end of the reproductive period and by examining in vitro effect of estradiol on Mϕ from young and middle-aged female AO rats. The results showed that: 1) the ability of Mϕ from AO females to “control” the resolution of acute inflammation changes during the early phase of reproductive aging, and these changes are strain-specific (Mϕ from middle-aged AO females that “age more successful” than Dark Agouti females, show properties which may be associated with better "control" of inflammation); 2) these changes are sex-specific (Mϕ from middle-aged females have a greater capacity to “control” inflammation than Mϕ from males of the same age group) and 3) both estradiol and progesterone play important roles in the ability of Mϕ from AO females to “control” acute inflammation. In vitro studies revealed that, in addition to changes in estradiol concentration, intrinsic changes in Mϕ that regulate their response to estradiol action are important for agedependent changes in Mϕ ability to „control“ inflammation.
PB  - Univerzitet u Beogradu, Farmaceutski fakultet
T2  - Univerzitet u Beogradu
T1  - Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju
UR  - https://hdl.handle.net/21.15107/rcub_intor_619
ER  - 
@phdthesis{
author = "Ćuruvija, Ivana D.",
year = "2021",
abstract = "Starenje se povezuje sa razvojem sistemskog, sterilnog hroničnog zapaljenja (engl. „inflammaging”). Malo je podataka o uticaju genetskih faktora i pola na sposobnost makrofaga (Mϕ), kao ključnih ćelija urođenog imunskog odgovora, da tokom starenja “kontrolišu” rezoluciju akutnog zapaljenja i time razvoj hroničnog zapaljenja. Ciljevi ove disertacije su bili da se ispita 1) uticaj rane faze reproduktivnog starenja na fenotipske osobine (ekspresija markera povezanih sa aktivacijom i poreklom/funkcijom) i funkcijska svojstva (fagocitoza, sinteza inflamatornih medijatora) Mϕ “mirne” i inflamirane (delovanjem tioglikolata) peritonealne duplje ženki Albino Oxford (AO) pacova, 2) značaj genetskih faktora za reproduktivnim starenjem uslovljene promene peritonealnih Mϕ od značaja za uspešnu rezoluciju akutnog zapaljenja i 3) uloga polnih steroida u nastanku ovih promena uporednom analizom promena kod mužjaka i ženki AO pacova, njihovom analizom kod ženki AO pacova kojima su na kraju reproduktivnog perioda uklonjeni jajnici i ispitivanjem delovanja estradiola na Mϕ mladih i sredovečnih ženki AO pacova in vitro. Rezultati su pokazali da: 1) se sposobnost Mϕ ženki AO pacova da “kontrolišu” rezoluciju akutnog zapaljenja menja već tokom rane faze reproduktivnog starenja, kao i da su ove promene sojno specifične (Mϕ sredovečnih ženki AO pacova koje “uspešnije” stare od ženki Dark Agouti pacova pokazuju svojstva koja se mogu povezati sa boljom “kontrolom” inflamacije); 2) su ove promene polno specifične (Mϕ sredovečnih ženki imaju svojstva koja ukazuju na veći kapacitet da “kontrolišu” inflamaciju od Mϕ mužjaka istog uzrasta) i 3) u nastanku promena relevantnih za sposobnost Mϕ ženki AO pacova da “kontrolišu” akutnu inflamaciju važnu ulogu imaju promene u delovanju i estradiola i progesterona. Dodatno, ispitavanja in vitro su ukazala da su za uzrasno zavisne promene u sposobnosti Mϕ da “kontrolišu” inflamaciju pored promene u koncentraciji estradiola važne i one u samim Mϕ, koje menjaju njihov odgovor na delovanje estradiola., Aging is associated with the development of systemic, sterile chronic inflammation ("inflammaging"). Little is known about the influence of genetic factors and sex on the ability of macrophages (Mϕ), as key innate immune cells, to "control" the resolution of acute inflammation and thus the development of chronic inflammation during aging. The objectives of this dissertation were to examine 1) the influence of the early phase of reproductive aging on phenotypic characteristics (expression of markers associated with activation and origin/function) and functional characteristics (phagocytosis, synthesis of inflammatory mediators) of Mϕ isolated from “naive” and inflamed (thioglycollate-induced) peritoneal cavity of females Albino Oxford (AO) rats; 2) the significance of genetic factors for reproductive aging-related changes of peritoneal Mϕ, especially those important for successful resolution of acute inflammation and 3) the role of sex steroids in the occurrence of these changes by comparative analysis in males and females of AO rats, their analysis in female AO rats whose ovaries were removed at the end of the reproductive period and by examining in vitro effect of estradiol on Mϕ from young and middle-aged female AO rats. The results showed that: 1) the ability of Mϕ from AO females to “control” the resolution of acute inflammation changes during the early phase of reproductive aging, and these changes are strain-specific (Mϕ from middle-aged AO females that “age more successful” than Dark Agouti females, show properties which may be associated with better "control" of inflammation); 2) these changes are sex-specific (Mϕ from middle-aged females have a greater capacity to “control” inflammation than Mϕ from males of the same age group) and 3) both estradiol and progesterone play important roles in the ability of Mϕ from AO females to “control” acute inflammation. In vitro studies revealed that, in addition to changes in estradiol concentration, intrinsic changes in Mϕ that regulate their response to estradiol action are important for agedependent changes in Mϕ ability to „control“ inflammation.",
publisher = "Univerzitet u Beogradu, Farmaceutski fakultet",
journal = "Univerzitet u Beogradu",
title = "Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju",
url = "https://hdl.handle.net/21.15107/rcub_intor_619"
}
Ćuruvija, I. D.. (2021). Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju. in Univerzitet u Beogradu
Univerzitet u Beogradu, Farmaceutski fakultet..
https://hdl.handle.net/21.15107/rcub_intor_619
Ćuruvija ID. Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju. in Univerzitet u Beogradu. 2021;.
https://hdl.handle.net/21.15107/rcub_intor_619 .
Ćuruvija, Ivana D., "Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju" in Univerzitet u Beogradu (2021),
https://hdl.handle.net/21.15107/rcub_intor_619 .

Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis

Dimitrijević, Mirjana; Arsenović-Ranin, Nevena; Kosec, Duško; Bufan, Biljana; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Leposavić, Gordana

(Nature Publishing Group, London, 2020)

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/554
AB  - The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-gamma /IL-4 production ratio was shifted towards IFN-gamma. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research.
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis
IS  - 1
VL  - 10
DO  - 10.1038/s41598-020-58127-y
ER  - 
@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana",
year = "2020",
abstract = "The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-gamma /IL-4 production ratio was shifted towards IFN-gamma. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis",
number = "1",
volume = "10",
doi = "10.1038/s41598-020-58127-y"
}
Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2020). Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis. in Scientific Reports
Nature Publishing Group, London., 10(1).
https://doi.org/10.1038/s41598-020-58127-y
Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis. in Scientific Reports. 2020;10(1).
doi:10.1038/s41598-020-58127-y .
Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis" in Scientific Reports, 10, no. 1 (2020),
https://doi.org/10.1038/s41598-020-58127-y . .
10
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Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

Pilipović, Ivan; Stojić-Vukanić, Zorica; Prijić, Ivana; Leposavić, Gordana

(Frontiers Media Sa, Lausanne, 2020)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Prijić, Ivana
AU  - Leposavić, Gordana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/571
AB  - The role of stress effector systems in the initiation and progression of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, has strongly been suggested. To corroborate this notion, alterations in activity of the sympathoadrenal and sympathoneural axes of sympathoadrenal system (a major communication pathway between the central nervous system and the immune system), mirrored in altered release of their end-point mediators (adrenaline and noradrenaline, respectively), are shown to precede (in MS) and/or occur during development of MS and EAE in response to immune cell activation (in early phase of disease) and disease-related damage of sympathoadrenal system neurons and their projections (in late phase of disease). To add to the complexity, innate immunity cells and T-lymphocytes synthesize noradrenaline that may be implicated in a local autocrine/paracrine self-amplifying feed-forward loop to enhance myeloid-cell synthesis of proinflammatory cytokines and inflammatory injury. Furthermore, experimental manipulations targeting noradrenaline/adrenaline action are shown to influence clinical outcome of EAE, in a disease phase-specific manner. This is partly related to the fact that virtually all types of cells involved in the instigation and progression of autoimmune inflammation and target tissue damage in EAE/MS express functional adrenoceptors. Although catecholamines exert majority of immunomodulatory effects through beta(2)-adrenoceptor, a role for alpha-adrenoceptors in EAE pathogenesis has also been indicated. In this review, we summarize all aforementioned aspects of immunopathogenetic action of catecholamines in EAE/MS as possibly important for designing new strategies targeting their action to prevent/mitigate autoimmune neuroinflammation and tissue damage.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Endocrinology
T1  - Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
VL  - 10
DO  - 10.3389/fendo.2019.00921
ER  - 
@article{
author = "Pilipović, Ivan and Stojić-Vukanić, Zorica and Prijić, Ivana and Leposavić, Gordana",
year = "2020",
abstract = "The role of stress effector systems in the initiation and progression of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, has strongly been suggested. To corroborate this notion, alterations in activity of the sympathoadrenal and sympathoneural axes of sympathoadrenal system (a major communication pathway between the central nervous system and the immune system), mirrored in altered release of their end-point mediators (adrenaline and noradrenaline, respectively), are shown to precede (in MS) and/or occur during development of MS and EAE in response to immune cell activation (in early phase of disease) and disease-related damage of sympathoadrenal system neurons and their projections (in late phase of disease). To add to the complexity, innate immunity cells and T-lymphocytes synthesize noradrenaline that may be implicated in a local autocrine/paracrine self-amplifying feed-forward loop to enhance myeloid-cell synthesis of proinflammatory cytokines and inflammatory injury. Furthermore, experimental manipulations targeting noradrenaline/adrenaline action are shown to influence clinical outcome of EAE, in a disease phase-specific manner. This is partly related to the fact that virtually all types of cells involved in the instigation and progression of autoimmune inflammation and target tissue damage in EAE/MS express functional adrenoceptors. Although catecholamines exert majority of immunomodulatory effects through beta(2)-adrenoceptor, a role for alpha-adrenoceptors in EAE pathogenesis has also been indicated. In this review, we summarize all aforementioned aspects of immunopathogenetic action of catecholamines in EAE/MS as possibly important for designing new strategies targeting their action to prevent/mitigate autoimmune neuroinflammation and tissue damage.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Endocrinology",
title = "Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis",
volume = "10",
doi = "10.3389/fendo.2019.00921"
}
Pilipović, I., Stojić-Vukanić, Z., Prijić, I.,& Leposavić, G.. (2020). Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. in Frontiers in Endocrinology
Frontiers Media Sa, Lausanne., 10.
https://doi.org/10.3389/fendo.2019.00921
Pilipović I, Stojić-Vukanić Z, Prijić I, Leposavić G. Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. in Frontiers in Endocrinology. 2020;10.
doi:10.3389/fendo.2019.00921 .
Pilipović, Ivan, Stojić-Vukanić, Zorica, Prijić, Ivana, Leposavić, Gordana, "Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis" in Frontiers in Endocrinology, 10 (2020),
https://doi.org/10.3389/fendo.2019.00921 . .
2
4
1
4

Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia

Pilipović, Ivan; Stojić-Vukanić, Zorica; Prijić, Ivana; Jasnić, Nebojša; Leposavić, Gordana

(Academic Press Inc Elsevier Science, San Diego, 2020)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Prijić, Ivana
AU  - Jasnić, Nebojša
AU  - Leposavić, Gordana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/561
AB  - Sympathetic dysfunction is suggested to contribute to development of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) alike. Considering important role of microglia in development/resolution of neuroinflammation, contribution of noradrenaline, the key sympathetic end-point mediator, in modulation of microglial phenotypic and functional properties in rat EAE model was examined. The study showed that noradrenaline acting in neurocrine and autocrine/paracrine way might influence microglia during EAE. Propranolol treatment over the effector phase moderated EAE course. This was associated with the increased proportion of microglia expressing CX3CR1, the key molecule in their immunomodulatory/neuroprotective action, and up regulation of CX3CR1 downstream Nrf2 gene. This correlated with the increased heme oxygenase-1 (HO-1) expression and phagocytic capacity of microglia, and their phenotypic changes mirrored in increased proportion of CD163- and CD83-expressing cells. The enhanced HO-1 expression was linked with the decreased proportion of microglial cells expressing IL-1 beta and IL-23, and possibly IL-6, followed by increased proportion of IL-10 expressing microglia, and downregulated MCP-1/CCL2 expression. Consistently, spinal cord infiltration with blood-borne myeloid and CD4 + T cells, as well as CD4 + T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17 + cells co-producing IFN-gamma and GM-CSF were decreased in propranolol-treated rats compared with saline-injected controls. The in vitro investigations of the effects of noradrenaline on microglia showed that noradrenaline through beta-adrenoceptor may influence Nrf2 expression also via CX3CR1-independent route. The study suggests beta-adrenoceptor-mediated neuroinflammation-promoting role of noradrenaline in EAE via modulation of microglial Nrf2 expression, and thereby forms the basis for further translational pharmacological research to improve multiple sclerosis therapy.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Neurobiology of Disease
T1  - Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia
VL  - 134
DO  - 10.1016/j.nbd.2019.104665
ER  - 
@article{
author = "Pilipović, Ivan and Stojić-Vukanić, Zorica and Prijić, Ivana and Jasnić, Nebojša and Leposavić, Gordana",
year = "2020",
abstract = "Sympathetic dysfunction is suggested to contribute to development of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) alike. Considering important role of microglia in development/resolution of neuroinflammation, contribution of noradrenaline, the key sympathetic end-point mediator, in modulation of microglial phenotypic and functional properties in rat EAE model was examined. The study showed that noradrenaline acting in neurocrine and autocrine/paracrine way might influence microglia during EAE. Propranolol treatment over the effector phase moderated EAE course. This was associated with the increased proportion of microglia expressing CX3CR1, the key molecule in their immunomodulatory/neuroprotective action, and up regulation of CX3CR1 downstream Nrf2 gene. This correlated with the increased heme oxygenase-1 (HO-1) expression and phagocytic capacity of microglia, and their phenotypic changes mirrored in increased proportion of CD163- and CD83-expressing cells. The enhanced HO-1 expression was linked with the decreased proportion of microglial cells expressing IL-1 beta and IL-23, and possibly IL-6, followed by increased proportion of IL-10 expressing microglia, and downregulated MCP-1/CCL2 expression. Consistently, spinal cord infiltration with blood-borne myeloid and CD4 + T cells, as well as CD4 + T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17 + cells co-producing IFN-gamma and GM-CSF were decreased in propranolol-treated rats compared with saline-injected controls. The in vitro investigations of the effects of noradrenaline on microglia showed that noradrenaline through beta-adrenoceptor may influence Nrf2 expression also via CX3CR1-independent route. The study suggests beta-adrenoceptor-mediated neuroinflammation-promoting role of noradrenaline in EAE via modulation of microglial Nrf2 expression, and thereby forms the basis for further translational pharmacological research to improve multiple sclerosis therapy.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Neurobiology of Disease",
title = "Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia",
volume = "134",
doi = "10.1016/j.nbd.2019.104665"
}
Pilipović, I., Stojić-Vukanić, Z., Prijić, I., Jasnić, N.,& Leposavić, G.. (2020). Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia. in Neurobiology of Disease
Academic Press Inc Elsevier Science, San Diego., 134.
https://doi.org/10.1016/j.nbd.2019.104665
Pilipović I, Stojić-Vukanić Z, Prijić I, Jasnić N, Leposavić G. Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia. in Neurobiology of Disease. 2020;134.
doi:10.1016/j.nbd.2019.104665 .
Pilipović, Ivan, Stojić-Vukanić, Zorica, Prijić, Ivana, Jasnić, Nebojša, Leposavić, Gordana, "Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia" in Neurobiology of Disease, 134 (2020),
https://doi.org/10.1016/j.nbd.2019.104665 . .
15
7
16

Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences

Bufan, Biljana; Arsenović-Ranin, Nevena; Petrović, Raisa; Živković, Irena; Stoiljković, Vera; Leposavić, Gordana

(Pergamon-Elsevier Science Ltd, Oxford, 2020)

TY  - JOUR
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/556
AB  - Considering variability in vaccine responsiveness across human populations, in respect to magnitude and quality, and importance of vaccines in the elderly, the influence of recipient genetic background on the kinetics of age-related changes in the serum IgG antibody responses to seasonal trivalent inactivated split-virus influenza bulk (TIV) was studied in BALB/c and C57BL/6 mice showing quantitative and qualitative differences in this responses in young adult ages. With ageing the total serum IgG response to influenza viruses declined, in a strain-specific manner, so the strain disparity observed in young adult mice (the greater magnitude of IgG response in BALB/c mice) disappeared in aged mice. However, the sexual dimorphisms in this response (more prominent in females of both strains) remained in aged ones. The strain-specific differences in age-related decline in the magnitude of IgG response to TIV correlated with the number of germinal centre (GC) B splenocytes. The agerelated decline in GC B cell number was consistent with the decrease in the proliferation of B cells and CD4 + cells in splenocyte cultures upon restimulation with TIV. Additionally, the age-related decrease in the magnitude of IgG response correlated with the increase in follicular T regulatory (fTreg)/follicular T helper (fTh) and fTreg/GC B splenocyte ratios (reflecting decrease in fTh and GC B numbers without changes in fTreg number), and the frequency of CD4 + splenocytes producing IL-21, a key factor in balancing the B cell and fTreg cell activity. With ageing the avidity of virus influenza-specific antibody increased in females of both strains. Moreover, ageing affected IgG2a/IgG1 and IgG2c/IgG1 ratios (reflecting Thl/Th2 balance) in male BALB/c mice and female C57BL/6 mice, respectively. Consequently, differently from young mice exhibiting the similar ratios in male and female mice, in aged female mice of both strains IgG2a(c)/IgG1 ratios were shifted towards a less effective IgG1 response (stimulated by IL-4 cytokines) compared with males. The age-related alterations in IgG subclass profiles in both strains correlated with those in IFN-gamma/IL-4 production level ratio in splenocyte cultures restimulated with TIV. These findings stimulate further research to formulate sex-specific strategies to improve efficacy of influenza vaccine in the elderly.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences
VL  - 133
DO  - 10.1016/j.exger.2020.110857
ER  - 
@article{
author = "Bufan, Biljana and Arsenović-Ranin, Nevena and Petrović, Raisa and Živković, Irena and Stoiljković, Vera and Leposavić, Gordana",
year = "2020",
abstract = "Considering variability in vaccine responsiveness across human populations, in respect to magnitude and quality, and importance of vaccines in the elderly, the influence of recipient genetic background on the kinetics of age-related changes in the serum IgG antibody responses to seasonal trivalent inactivated split-virus influenza bulk (TIV) was studied in BALB/c and C57BL/6 mice showing quantitative and qualitative differences in this responses in young adult ages. With ageing the total serum IgG response to influenza viruses declined, in a strain-specific manner, so the strain disparity observed in young adult mice (the greater magnitude of IgG response in BALB/c mice) disappeared in aged mice. However, the sexual dimorphisms in this response (more prominent in females of both strains) remained in aged ones. The strain-specific differences in age-related decline in the magnitude of IgG response to TIV correlated with the number of germinal centre (GC) B splenocytes. The agerelated decline in GC B cell number was consistent with the decrease in the proliferation of B cells and CD4 + cells in splenocyte cultures upon restimulation with TIV. Additionally, the age-related decrease in the magnitude of IgG response correlated with the increase in follicular T regulatory (fTreg)/follicular T helper (fTh) and fTreg/GC B splenocyte ratios (reflecting decrease in fTh and GC B numbers without changes in fTreg number), and the frequency of CD4 + splenocytes producing IL-21, a key factor in balancing the B cell and fTreg cell activity. With ageing the avidity of virus influenza-specific antibody increased in females of both strains. Moreover, ageing affected IgG2a/IgG1 and IgG2c/IgG1 ratios (reflecting Thl/Th2 balance) in male BALB/c mice and female C57BL/6 mice, respectively. Consequently, differently from young mice exhibiting the similar ratios in male and female mice, in aged female mice of both strains IgG2a(c)/IgG1 ratios were shifted towards a less effective IgG1 response (stimulated by IL-4 cytokines) compared with males. The age-related alterations in IgG subclass profiles in both strains correlated with those in IFN-gamma/IL-4 production level ratio in splenocyte cultures restimulated with TIV. These findings stimulate further research to formulate sex-specific strategies to improve efficacy of influenza vaccine in the elderly.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences",
volume = "133",
doi = "10.1016/j.exger.2020.110857"
}
Bufan, B., Arsenović-Ranin, N., Petrović, R., Živković, I., Stoiljković, V.,& Leposavić, G.. (2020). Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 133.
https://doi.org/10.1016/j.exger.2020.110857
Bufan B, Arsenović-Ranin N, Petrović R, Živković I, Stoiljković V, Leposavić G. Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences. in Experimental Gerontology. 2020;133.
doi:10.1016/j.exger.2020.110857 .
Bufan, Biljana, Arsenović-Ranin, Nevena, Petrović, Raisa, Živković, Irena, Stoiljković, Vera, Leposavić, Gordana, "Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences" in Experimental Gerontology, 133 (2020),
https://doi.org/10.1016/j.exger.2020.110857 . .
1
5
3
5

Age and sex determine CD4+T cell stimulatory and polarizing capacity of rat splenic dendritic cells

Stojić-Vukanić, Zorica; Pilipović, Ivan; Bufan, Biljana; Stojanović, Marija; Leposavić, Gordana

(Springer, New York, 2020)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Bufan, Biljana
AU  - Stojanović, Marija
AU  - Leposavić, Gordana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/560
AB  - The study investigated influence of sex and age on splenic myeloid dendritic cells (DCs) from Dark Agouti rats. Freshly isolated DCs from young males exhibited less mature phenotype and greater endocytic capacity compared with those from age-matched females. Upon LPS stimulation in vitro they were less potent in stimulating allogeneic CD4+ cells in mixed leukocyte reaction (MLR), due to lower expression of MHC II, and greater NO and IL-10 production. In accordance with higher TGF-beta production, young male rat DCs were less potent in stimulating IL-17 production in MLR than those from young females. Irrespective of sex, endocytic capacity and responsiveness of DCs to LPS stimulation in culture, judging by their allostimulatory capacity in MLR decreased with age, reflecting decline in MHC II surface density followed by their greater NO production; the effects more prominent in females. Additionally, compared with LPS-stimulated DCs from young rats, those from sex-matched aged rats were more potent in stimulating IL-10 production in MLR, whereas capacity of DCs from aged female and male rats to stimulate IL-17 production remained unaltered and decreased, respectively. This reflected age-related shift in IL-6/TGF-beta production level ratio in LPS-stimulated DC cultures towards TGF-beta, and sex-specific age-related remodeling CD4+ cell cytokine pathways. Additionally, compared with LPS-stimulated DCs from young rats, those cells from sex-matched aged rats were less potent in stimulating IFN-gamma production in MLR, the effect particularly prominent in MLRs encompassing male rat DCs. The study showed that stimulatory and polarizing capacity of DCs depends on rat sex and age.
PB  - Springer, New York
T2  - Biogerontology
T1  - Age and sex determine CD4+T cell stimulatory and polarizing capacity of rat splenic dendritic cells
EP  - 107
IS  - 1
SP  - 83
VL  - 21
DO  - 10.1007/s10522-019-09845-y
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Bufan, Biljana and Stojanović, Marija and Leposavić, Gordana",
year = "2020",
abstract = "The study investigated influence of sex and age on splenic myeloid dendritic cells (DCs) from Dark Agouti rats. Freshly isolated DCs from young males exhibited less mature phenotype and greater endocytic capacity compared with those from age-matched females. Upon LPS stimulation in vitro they were less potent in stimulating allogeneic CD4+ cells in mixed leukocyte reaction (MLR), due to lower expression of MHC II, and greater NO and IL-10 production. In accordance with higher TGF-beta production, young male rat DCs were less potent in stimulating IL-17 production in MLR than those from young females. Irrespective of sex, endocytic capacity and responsiveness of DCs to LPS stimulation in culture, judging by their allostimulatory capacity in MLR decreased with age, reflecting decline in MHC II surface density followed by their greater NO production; the effects more prominent in females. Additionally, compared with LPS-stimulated DCs from young rats, those from sex-matched aged rats were more potent in stimulating IL-10 production in MLR, whereas capacity of DCs from aged female and male rats to stimulate IL-17 production remained unaltered and decreased, respectively. This reflected age-related shift in IL-6/TGF-beta production level ratio in LPS-stimulated DC cultures towards TGF-beta, and sex-specific age-related remodeling CD4+ cell cytokine pathways. Additionally, compared with LPS-stimulated DCs from young rats, those cells from sex-matched aged rats were less potent in stimulating IFN-gamma production in MLR, the effect particularly prominent in MLRs encompassing male rat DCs. The study showed that stimulatory and polarizing capacity of DCs depends on rat sex and age.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Age and sex determine CD4+T cell stimulatory and polarizing capacity of rat splenic dendritic cells",
pages = "107-83",
number = "1",
volume = "21",
doi = "10.1007/s10522-019-09845-y"
}
Stojić-Vukanić, Z., Pilipović, I., Bufan, B., Stojanović, M.,& Leposavić, G.. (2020). Age and sex determine CD4+T cell stimulatory and polarizing capacity of rat splenic dendritic cells. in Biogerontology
Springer, New York., 21(1), 83-107.
https://doi.org/10.1007/s10522-019-09845-y
Stojić-Vukanić Z, Pilipović I, Bufan B, Stojanović M, Leposavić G. Age and sex determine CD4+T cell stimulatory and polarizing capacity of rat splenic dendritic cells. in Biogerontology. 2020;21(1):83-107.
doi:10.1007/s10522-019-09845-y .
Stojić-Vukanić, Zorica, Pilipović, Ivan, Bufan, Biljana, Stojanović, Marija, Leposavić, Gordana, "Age and sex determine CD4+T cell stimulatory and polarizing capacity of rat splenic dendritic cells" in Biogerontology, 21, no. 1 (2020):83-107,
https://doi.org/10.1007/s10522-019-09845-y . .
1
1
1

Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia

Pilipović, Ivan; Prijić, Ivana; Stojić-Vukanić, Zorica; Leposavić, Gordana

(Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, 2019)

TY  - CONF
AU  - Pilipović, Ivan
AU  - Prijić, Ivana
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/854
AB  - Sympathetic dysfunction was proposed to participate in development of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). This may be linked with findings indicating that noradrenaline, the key sympathetic end-point mediator, through β- adrenoceptor exerts immunomodulatory action. Considering importance of the target tissue for the clinical outcome of EAE, the study investigated the effects of propranolol, a non-selective β- adrenoceptor blocker, on the disease severity in Dark Agouti rats. Administration of propranolol over the effector phase of EAE substantially moderated neurological symptoms of the disease. This correlated with the increased proportion of spinal cord microglia expressing CX3CR1, the crucial neuroinflammation-limiting molecule, and upregulated expression of Nrf2, the key CX3CR1 downstream target gene. Additionally, in spinal cord of propranolol-administered rats the expression of heme-oxigenase 1, Nrf2 target gene, was upregulated. Consequently, microglia from propranolol-administered rats, exhibited increased proportion of IL-10–expressing cells, but decreased those of IL-1β– and IL-23–expressing ones. Propranolol also downregulated the IL-6 and MCP-1/CCL2 expression in spinal cord. Furthermore, propranolol affecting CXCR1/Nrf2 signaling pathway enhanced microglial phagocytic/endocytic capacity and surface expression of anti-inflammatory CD163/CD83 markers. Results from in vitro pharmacological study examining influence of noradrenaline/propranolol on functional properties of microglia showed that microglia synthesize noradrenaline, which, in turn, through β-adrenoceptor, downregulated their Nrf2 expression, in a CX3CR1-independent manner. In accordance with microglial shift towards a more anti-inflammatory profile, in spinal cord of propranolol- administered rats was found: i) decreased infiltration with blood-borne myeloid and CD4+ T cells, and ii) reduced CD4+ T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17+ cells co-producing IFN-y and GM-CSF. The study suggests a neuroinflammation-promoting role for central noradrenaline in EAE, via β-adrenoceptor– mediated modulation of microglial Nrf2 expression. Thus, it points out to a putative target for future translational pharmacological research to optimize multiple sclerosis therapy.
PB  - Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade
PB  - Immunological Society of Serbia
C3  - Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019
T1  - Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia
EP  - 69
SP  - 69
UR  - https://hdl.handle.net/21.15107/rcub_intor_854
ER  - 
@conference{
author = "Pilipović, Ivan and Prijić, Ivana and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2019",
abstract = "Sympathetic dysfunction was proposed to participate in development of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). This may be linked with findings indicating that noradrenaline, the key sympathetic end-point mediator, through β- adrenoceptor exerts immunomodulatory action. Considering importance of the target tissue for the clinical outcome of EAE, the study investigated the effects of propranolol, a non-selective β- adrenoceptor blocker, on the disease severity in Dark Agouti rats. Administration of propranolol over the effector phase of EAE substantially moderated neurological symptoms of the disease. This correlated with the increased proportion of spinal cord microglia expressing CX3CR1, the crucial neuroinflammation-limiting molecule, and upregulated expression of Nrf2, the key CX3CR1 downstream target gene. Additionally, in spinal cord of propranolol-administered rats the expression of heme-oxigenase 1, Nrf2 target gene, was upregulated. Consequently, microglia from propranolol-administered rats, exhibited increased proportion of IL-10–expressing cells, but decreased those of IL-1β– and IL-23–expressing ones. Propranolol also downregulated the IL-6 and MCP-1/CCL2 expression in spinal cord. Furthermore, propranolol affecting CXCR1/Nrf2 signaling pathway enhanced microglial phagocytic/endocytic capacity and surface expression of anti-inflammatory CD163/CD83 markers. Results from in vitro pharmacological study examining influence of noradrenaline/propranolol on functional properties of microglia showed that microglia synthesize noradrenaline, which, in turn, through β-adrenoceptor, downregulated their Nrf2 expression, in a CX3CR1-independent manner. In accordance with microglial shift towards a more anti-inflammatory profile, in spinal cord of propranolol- administered rats was found: i) decreased infiltration with blood-borne myeloid and CD4+ T cells, and ii) reduced CD4+ T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17+ cells co-producing IFN-y and GM-CSF. The study suggests a neuroinflammation-promoting role for central noradrenaline in EAE, via β-adrenoceptor– mediated modulation of microglial Nrf2 expression. Thus, it points out to a putative target for future translational pharmacological research to optimize multiple sclerosis therapy.",
publisher = "Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Immunological Society of Serbia",
journal = "Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019",
title = "Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia",
pages = "69-69",
url = "https://hdl.handle.net/21.15107/rcub_intor_854"
}
Pilipović, I., Prijić, I., Stojić-Vukanić, Z.,& Leposavić, G.. (2019). Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia. in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019
Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade., 69-69.
https://hdl.handle.net/21.15107/rcub_intor_854
Pilipović I, Prijić I, Stojić-Vukanić Z, Leposavić G. Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia. in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019. 2019;:69-69.
https://hdl.handle.net/21.15107/rcub_intor_854 .
Pilipović, Ivan, Prijić, Ivana, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia" in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019 (2019):69-69,
https://hdl.handle.net/21.15107/rcub_intor_854 .

Sexual dimorphism in thymic senescence

Nacka-Aleksić, Mirjana; Pilipović, Ivan; Kotur-Stevuljević, Jelena; Leposavić, Gordana

(Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, 2019)

TY  - CONF
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Kotur-Stevuljević, Jelena
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/855
AB  - The study showed sexual dimorphism in the kinetics of thymic involution in Dark Agouti rats, so in 24-month-old males prominent thymic fibro-adipose degeneration was found, whereas fibrous changes dominated in thymi of age-matched females. This dimorphism reflected sex-specific constellation of age-related alterations in the expression of the key proadipogenic factors (xanthine oxidase-induced PPARy, STAT3, the transcription factor controlling PPARy downstream adipocyte- differentiation-related gene expression, and IL-6) and TGF-β, the key pro-fibrinogenic factor. The age-related epithelial-mesenchymal transition in thymi of Dark Agouti rats was accompanied by decline in thymopoiesis mirrored in decrease in the frequency of the most mature CD4+CD8-/CD4-CD8+ TCRaβhigh thymocytes and CD4+ and CD8+ recent thymic emigrants in peripheral blood (PB). This was more prominent in males than in females. Irrespective of sex, differentiation/maturation “block” leading to accumulation of the least mature CD45RC+CD2-CD4-CD8- thymocytes, accompanied by decline in the frequency of descendant double positive (DP) TCRaβ- ones was observed with aging. This was followed by opposing changes in the efficacy of positive/negative selection in males and females, which was related to sex-specific alterations in thymic expression of Nur77, a nuclear receptor involved in negative selection, and surface density of CD90 (negative regulator of thymocyte-selection threshold) on thymocytes undergoing selection. Moreover, compared with old females, in age-matched males CD4+CD8-/CD4-CD8+ TCRaβhigh thymocyte ratio was shifted towards the latter. However, CD4+/CD8+ ratio in PB was skewed towards CD8+ T cells in both sexes. Irrespective of sex, with aging the frequency of CD4+CD25+Foxp3+ thymocytes diminished, but that of CD4+CD25+Foxp3+ T regulatory cells (Tregs) in PB increased, most likely due to enhanced expansion of “induced” Tregs. Collectively, the study i) indicates necessity of sex-specific approaches in designing thymus-rejuvenating strategies and ii) warns that changes in the PB T-cell compartment do not necessarily reflect sex-based differences in T-cell generation in thymus.
PB  - Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade
PB  - Immunological Society of Serbia
C3  - Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019
T1  - Sexual dimorphism in thymic senescence
EP  - 85
SP  - 85
UR  - https://hdl.handle.net/21.15107/rcub_intor_855
ER  - 
@conference{
author = "Nacka-Aleksić, Mirjana and Pilipović, Ivan and Kotur-Stevuljević, Jelena and Leposavić, Gordana",
year = "2019",
abstract = "The study showed sexual dimorphism in the kinetics of thymic involution in Dark Agouti rats, so in 24-month-old males prominent thymic fibro-adipose degeneration was found, whereas fibrous changes dominated in thymi of age-matched females. This dimorphism reflected sex-specific constellation of age-related alterations in the expression of the key proadipogenic factors (xanthine oxidase-induced PPARy, STAT3, the transcription factor controlling PPARy downstream adipocyte- differentiation-related gene expression, and IL-6) and TGF-β, the key pro-fibrinogenic factor. The age-related epithelial-mesenchymal transition in thymi of Dark Agouti rats was accompanied by decline in thymopoiesis mirrored in decrease in the frequency of the most mature CD4+CD8-/CD4-CD8+ TCRaβhigh thymocytes and CD4+ and CD8+ recent thymic emigrants in peripheral blood (PB). This was more prominent in males than in females. Irrespective of sex, differentiation/maturation “block” leading to accumulation of the least mature CD45RC+CD2-CD4-CD8- thymocytes, accompanied by decline in the frequency of descendant double positive (DP) TCRaβ- ones was observed with aging. This was followed by opposing changes in the efficacy of positive/negative selection in males and females, which was related to sex-specific alterations in thymic expression of Nur77, a nuclear receptor involved in negative selection, and surface density of CD90 (negative regulator of thymocyte-selection threshold) on thymocytes undergoing selection. Moreover, compared with old females, in age-matched males CD4+CD8-/CD4-CD8+ TCRaβhigh thymocyte ratio was shifted towards the latter. However, CD4+/CD8+ ratio in PB was skewed towards CD8+ T cells in both sexes. Irrespective of sex, with aging the frequency of CD4+CD25+Foxp3+ thymocytes diminished, but that of CD4+CD25+Foxp3+ T regulatory cells (Tregs) in PB increased, most likely due to enhanced expansion of “induced” Tregs. Collectively, the study i) indicates necessity of sex-specific approaches in designing thymus-rejuvenating strategies and ii) warns that changes in the PB T-cell compartment do not necessarily reflect sex-based differences in T-cell generation in thymus.",
publisher = "Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Immunological Society of Serbia",
journal = "Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019",
title = "Sexual dimorphism in thymic senescence",
pages = "85-85",
url = "https://hdl.handle.net/21.15107/rcub_intor_855"
}
Nacka-Aleksić, M., Pilipović, I., Kotur-Stevuljević, J.,& Leposavić, G.. (2019). Sexual dimorphism in thymic senescence. in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019
Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade., 85-85.
https://hdl.handle.net/21.15107/rcub_intor_855
Nacka-Aleksić M, Pilipović I, Kotur-Stevuljević J, Leposavić G. Sexual dimorphism in thymic senescence. in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019. 2019;:85-85.
https://hdl.handle.net/21.15107/rcub_intor_855 .
Nacka-Aleksić, Mirjana, Pilipović, Ivan, Kotur-Stevuljević, Jelena, Leposavić, Gordana, "Sexual dimorphism in thymic senescence" in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019 (2019):85-85,
https://hdl.handle.net/21.15107/rcub_intor_855 .

Sexual dimorphism in the severity of rat collagen-induced arthritis: the relevance of T follicular cell help to B cells

Dimitrijević, Mirjana; Arsenović-Ranin, Nevena; Kosec, Duško; Bufan, Biljana; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Leposavić, Gordana

(Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, 2019)

TY  - CONF
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/856
AB  - Collagen-induced arthritis (CIA) is a well-established experimental model mimicking many immunopathogenic and clinical aspects of rheumatoid arthritis (RA), including sexual dimorphism in the clinical presentation. Our previous study showed that a more severe disease in female compared with male rats correlated with more robust Th17 response reflecting sexual dimorphism in Th17/Treg axis plasticity. Given that autoantibodies play a significant role in the immunopathogenesis of RA and CIA, in the present study the germinal center (GC) reaction in the lymph nodes draining inflamed joints and adjacent tissue (dLNs) was examined for putative sexual dimorphism. Female rats mounted greater serum collagen II-specific IgG response than their male counterparts. This dimorphism correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki67+ cells among dLN B cells was higher in females than in males. This was associated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL- 21/27, the key cytokines involved in Tfh cell generation and help to B cells. Additionally, in collagen II-stimulated female rat dLN cell cultures, IFN-γ/IL-4 ratio was shifted towards IFN-γ. Consistently, serum ratio between pathogenic IgG2a and protective IgG1 collagen II-specific antibodies was shifted towards the former in females. Thus, the study suggests that targeting T/B cell interactions should be considered in further translation research aimed to design sex-specific therapies for RA.
PB  - Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade
PB  - Immunological Society of Serbia
C3  - Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019
T1  - Sexual dimorphism in the severity of rat collagen-induced arthritis: the relevance of T follicular cell help to B cells
EP  - 106
SP  - 106
UR  - https://hdl.handle.net/21.15107/rcub_intor_856
ER  - 
@conference{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana",
year = "2019",
abstract = "Collagen-induced arthritis (CIA) is a well-established experimental model mimicking many immunopathogenic and clinical aspects of rheumatoid arthritis (RA), including sexual dimorphism in the clinical presentation. Our previous study showed that a more severe disease in female compared with male rats correlated with more robust Th17 response reflecting sexual dimorphism in Th17/Treg axis plasticity. Given that autoantibodies play a significant role in the immunopathogenesis of RA and CIA, in the present study the germinal center (GC) reaction in the lymph nodes draining inflamed joints and adjacent tissue (dLNs) was examined for putative sexual dimorphism. Female rats mounted greater serum collagen II-specific IgG response than their male counterparts. This dimorphism correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki67+ cells among dLN B cells was higher in females than in males. This was associated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL- 21/27, the key cytokines involved in Tfh cell generation and help to B cells. Additionally, in collagen II-stimulated female rat dLN cell cultures, IFN-γ/IL-4 ratio was shifted towards IFN-γ. Consistently, serum ratio between pathogenic IgG2a and protective IgG1 collagen II-specific antibodies was shifted towards the former in females. Thus, the study suggests that targeting T/B cell interactions should be considered in further translation research aimed to design sex-specific therapies for RA.",
publisher = "Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Immunological Society of Serbia",
journal = "Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019",
title = "Sexual dimorphism in the severity of rat collagen-induced arthritis: the relevance of T follicular cell help to B cells",
pages = "106-106",
url = "https://hdl.handle.net/21.15107/rcub_intor_856"
}
Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2019). Sexual dimorphism in the severity of rat collagen-induced arthritis: the relevance of T follicular cell help to B cells. in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019
Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade., 106-106.
https://hdl.handle.net/21.15107/rcub_intor_856
Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sexual dimorphism in the severity of rat collagen-induced arthritis: the relevance of T follicular cell help to B cells. in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019. 2019;:106-106.
https://hdl.handle.net/21.15107/rcub_intor_856 .
Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sexual dimorphism in the severity of rat collagen-induced arthritis: the relevance of T follicular cell help to B cells" in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019 (2019):106-106,
https://hdl.handle.net/21.15107/rcub_intor_856 .

Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis

Pilipović, Ivan; Vujnović, Ivana; Petrović, Raisa; Stojić-Vukanić, Zorica; Leposavić, Gordana

(Karger, Basel, 2019)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Petrović, Raisa
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/541
AB  - Objective: We examined the effect of beta-adrenoceptor (AR) blockade in the preclinical phase of experimental autoimmune encephalomyelitis (EAE), the most commonly used model of multiple sclerosis, on the development of primary CD4+ T-cell responses in draining lymph nodes (dLNs). Methods: CD11b+ cell migration to dLNs, CD4+ T-cell activation/proliferation, and IL-17+ CD4+ (Th17) cell numbers in dLN and spinal cord (SC) were examined in male and female Dark Agouti rats using flow cytometry analysis. Results: Irrespective of sex, in propranolol-treated (PT) rats, migration of CD11b+ antigen-presenting cells from the site of immunization to dLNs was impaired compared with saline-treated controls and consequently the frequency of all CD11b+ cells in dLNs and activated cells among them, too. This correlated with decreased expression of CCL19/21 transcripts in dLNs. Consistently, the frequency of activated/proliferating cells among dLN CD4+ T cells was reduced in PT rats. Additionally, propranolol reduced the number of Th17 cells in dLNs and SC. Consistently, male and female PT rats exhibited a decreased incidence of EAE and prolonged duration of the asymptomatic disease phase. Conclusion: This study suggests that sympathetic dysregulation is involved in the outbreak of clinical EAE. (C) 2019 S. Karger AG, Basel
PB  - Karger, Basel
T2  - Neuroimmunomodulation
T1  - Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis
EP  - 138
IS  - 3
SP  - 129
VL  - 26
DO  - 10.1159/000500094
ER  - 
@article{
author = "Pilipović, Ivan and Vujnović, Ivana and Petrović, Raisa and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2019",
abstract = "Objective: We examined the effect of beta-adrenoceptor (AR) blockade in the preclinical phase of experimental autoimmune encephalomyelitis (EAE), the most commonly used model of multiple sclerosis, on the development of primary CD4+ T-cell responses in draining lymph nodes (dLNs). Methods: CD11b+ cell migration to dLNs, CD4+ T-cell activation/proliferation, and IL-17+ CD4+ (Th17) cell numbers in dLN and spinal cord (SC) were examined in male and female Dark Agouti rats using flow cytometry analysis. Results: Irrespective of sex, in propranolol-treated (PT) rats, migration of CD11b+ antigen-presenting cells from the site of immunization to dLNs was impaired compared with saline-treated controls and consequently the frequency of all CD11b+ cells in dLNs and activated cells among them, too. This correlated with decreased expression of CCL19/21 transcripts in dLNs. Consistently, the frequency of activated/proliferating cells among dLN CD4+ T cells was reduced in PT rats. Additionally, propranolol reduced the number of Th17 cells in dLNs and SC. Consistently, male and female PT rats exhibited a decreased incidence of EAE and prolonged duration of the asymptomatic disease phase. Conclusion: This study suggests that sympathetic dysregulation is involved in the outbreak of clinical EAE. (C) 2019 S. Karger AG, Basel",
publisher = "Karger, Basel",
journal = "Neuroimmunomodulation",
title = "Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis",
pages = "138-129",
number = "3",
volume = "26",
doi = "10.1159/000500094"
}
Pilipović, I., Vujnović, I., Petrović, R., Stojić-Vukanić, Z.,& Leposavić, G.. (2019). Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis. in Neuroimmunomodulation
Karger, Basel., 26(3), 129-138.
https://doi.org/10.1159/000500094
Pilipović I, Vujnović I, Petrović R, Stojić-Vukanić Z, Leposavić G. Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis. in Neuroimmunomodulation. 2019;26(3):129-138.
doi:10.1159/000500094 .
Pilipović, Ivan, Vujnović, Ivana, Petrović, Raisa, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis" in Neuroimmunomodulation, 26, no. 3 (2019):129-138,
https://doi.org/10.1159/000500094 . .
6
3
6

Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?

Vujnović, Ivana; Pilipović, Ivan; Jasnić, Nebojša; Petrović, Raisa; Blagojević, Veljko; Arsenović-Ranin, Nevena; Stojić-Vukanić, Zorica; Đorđević, Jelena; Leposavić, Gordana

(Academic Press Inc Elsevier Science, San Diego, 2019)

TY  - JOUR
AU  - Vujnović, Ivana
AU  - Pilipović, Ivan
AU  - Jasnić, Nebojša
AU  - Petrović, Raisa
AU  - Blagojević, Veljko
AU  - Arsenović-Ranin, Nevena
AU  - Stojić-Vukanić, Zorica
AU  - Đorđević, Jelena
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/539
AB  - Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4 + T-cell (auto) immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (beta-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4 + T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of beta(2)-adrenoceptor-expressing CD4 + T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4 + lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1 beta and IL-23/p19 expression and IL-17 + CD4 + cell frequency, but enhanced IL-17 production only in male rat CD4 + lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, beta-adrenoceptor-mediated signalling may contribute to sex bias in rat IL-17-producing cell secretory capacity.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Cellular Immunology
T1  - Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?
EP  - 57
SP  - 48
VL  - 336
DO  - 10.1016/j.cellimm.2018.12.009
ER  - 
@article{
author = "Vujnović, Ivana and Pilipović, Ivan and Jasnić, Nebojša and Petrović, Raisa and Blagojević, Veljko and Arsenović-Ranin, Nevena and Stojić-Vukanić, Zorica and Đorđević, Jelena and Leposavić, Gordana",
year = "2019",
abstract = "Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4 + T-cell (auto) immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (beta-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4 + T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of beta(2)-adrenoceptor-expressing CD4 + T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4 + lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1 beta and IL-23/p19 expression and IL-17 + CD4 + cell frequency, but enhanced IL-17 production only in male rat CD4 + lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, beta-adrenoceptor-mediated signalling may contribute to sex bias in rat IL-17-producing cell secretory capacity.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Cellular Immunology",
title = "Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?",
pages = "57-48",
volume = "336",
doi = "10.1016/j.cellimm.2018.12.009"
}
Vujnović, I., Pilipović, I., Jasnić, N., Petrović, R., Blagojević, V., Arsenović-Ranin, N., Stojić-Vukanić, Z., Đorđević, J.,& Leposavić, G.. (2019). Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?. in Cellular Immunology
Academic Press Inc Elsevier Science, San Diego., 336, 48-57.
https://doi.org/10.1016/j.cellimm.2018.12.009
Vujnović I, Pilipović I, Jasnić N, Petrović R, Blagojević V, Arsenović-Ranin N, Stojić-Vukanić Z, Đorđević J, Leposavić G. Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?. in Cellular Immunology. 2019;336:48-57.
doi:10.1016/j.cellimm.2018.12.009 .
Vujnović, Ivana, Pilipović, Ivan, Jasnić, Nebojša, Petrović, Raisa, Blagojević, Veljko, Arsenović-Ranin, Nevena, Stojić-Vukanić, Zorica, Đorđević, Jelena, Leposavić, Gordana, "Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?" in Cellular Immunology, 336 (2019):48-57,
https://doi.org/10.1016/j.cellimm.2018.12.009 . .
1
14
9
13

Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor

Pilipović, Ivan; Vujnović, Ivana; Stojić-Vukanić, Zorica; Petrović, Raisa; Kosec, Duško; Nacka-Aleksić, Mirjana; Jasnić, Nebojša; Leposavić, Gordana

(Humana Press Inc, Totowa, 2019)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Stojić-Vukanić, Zorica
AU  - Petrović, Raisa
AU  - Kosec, Duško
AU  - Nacka-Aleksić, Mirjana
AU  - Jasnić, Nebojša
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/531
AB  - Pharmacological blockade of alpha(1)-adrenoceptor is shown to influence development of experimental autoimmune encephalomyelitis (EAE), an IL-17-producing CD4+TCR+ (Th17) cell-mediated disease mimicking multiple sclerosis. Considering significance of CD4+ cell priming for the clinical outcome of EAE, the study examined alpha(1)-adrenoceptor-mediated influence of catecholamines, particularly those derived from draining lymph node (dLN) cells (as catecholamine supply from nerve fibers decreases with the initiation of autoimmune diseases) for CD4+ cell priming. The results confirmed diminishing effect of immunization on nerve fiber-derived noradrenaline supply and showed that antigen presenting and CD4+ cells synthesize catecholamines, while antigen presenting cells and only CD4+CD25+Foxp3+ regulatory T cells (Tregs) express alpha(1)-adrenoceptor. The analysis of influence of alpha(1)-adrenoceptor antagonist prazosin on the myelin basic protein (MBP)-stimulated CD4+ lymphocytes in dLN cell culture showed their diminished proliferation in the presence of prazosin. This was consistent with prazosin enhancing effect on Treg frequency and their Foxp3 expression in these cultures. The latter was associated with upregulation of TGF-beta expression. Additionally, prazosin decreased antigen presenting cell activation and affected their cytokine profile by diminishing the frequency of cells that produce Th17 polarizing cytokines (IL-1 beta and IL-23) and increasing that of IL-10-producing cells. Consistently, the frequency of all IL-17A+ cells and those co-expressing GM-CSF within CD4+ lymphocytes was decreased in prazosin-supplemented MBP-stimulated dLN cell cultures. Collectively, the results indicated that dLN cell-derived catecholamines may influence EAE development by modulating interactions between distinct subtypes of CD4+ T cells and antigen presenting cells through alpha(1)-adrenoceptor and consequently CD4+ T cell priming.
PB  - Humana Press Inc, Totowa
T2  - Immunologic Research
T1  - Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor
EP  - 240
IS  - 2-3
SP  - 223
VL  - 67
DO  - 10.1007/s12026-019-09082-y
ER  - 
@article{
author = "Pilipović, Ivan and Vujnović, Ivana and Stojić-Vukanić, Zorica and Petrović, Raisa and Kosec, Duško and Nacka-Aleksić, Mirjana and Jasnić, Nebojša and Leposavić, Gordana",
year = "2019",
abstract = "Pharmacological blockade of alpha(1)-adrenoceptor is shown to influence development of experimental autoimmune encephalomyelitis (EAE), an IL-17-producing CD4+TCR+ (Th17) cell-mediated disease mimicking multiple sclerosis. Considering significance of CD4+ cell priming for the clinical outcome of EAE, the study examined alpha(1)-adrenoceptor-mediated influence of catecholamines, particularly those derived from draining lymph node (dLN) cells (as catecholamine supply from nerve fibers decreases with the initiation of autoimmune diseases) for CD4+ cell priming. The results confirmed diminishing effect of immunization on nerve fiber-derived noradrenaline supply and showed that antigen presenting and CD4+ cells synthesize catecholamines, while antigen presenting cells and only CD4+CD25+Foxp3+ regulatory T cells (Tregs) express alpha(1)-adrenoceptor. The analysis of influence of alpha(1)-adrenoceptor antagonist prazosin on the myelin basic protein (MBP)-stimulated CD4+ lymphocytes in dLN cell culture showed their diminished proliferation in the presence of prazosin. This was consistent with prazosin enhancing effect on Treg frequency and their Foxp3 expression in these cultures. The latter was associated with upregulation of TGF-beta expression. Additionally, prazosin decreased antigen presenting cell activation and affected their cytokine profile by diminishing the frequency of cells that produce Th17 polarizing cytokines (IL-1 beta and IL-23) and increasing that of IL-10-producing cells. Consistently, the frequency of all IL-17A+ cells and those co-expressing GM-CSF within CD4+ lymphocytes was decreased in prazosin-supplemented MBP-stimulated dLN cell cultures. Collectively, the results indicated that dLN cell-derived catecholamines may influence EAE development by modulating interactions between distinct subtypes of CD4+ T cells and antigen presenting cells through alpha(1)-adrenoceptor and consequently CD4+ T cell priming.",
publisher = "Humana Press Inc, Totowa",
journal = "Immunologic Research",
title = "Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor",
pages = "240-223",
number = "2-3",
volume = "67",
doi = "10.1007/s12026-019-09082-y"
}
Pilipović, I., Vujnović, I., Stojić-Vukanić, Z., Petrović, R., Kosec, D., Nacka-Aleksić, M., Jasnić, N.,& Leposavić, G.. (2019). Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor. in Immunologic Research
Humana Press Inc, Totowa., 67(2-3), 223-240.
https://doi.org/10.1007/s12026-019-09082-y
Pilipović I, Vujnović I, Stojić-Vukanić Z, Petrović R, Kosec D, Nacka-Aleksić M, Jasnić N, Leposavić G. Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor. in Immunologic Research. 2019;67(2-3):223-240.
doi:10.1007/s12026-019-09082-y .
Pilipović, Ivan, Vujnović, Ivana, Stojić-Vukanić, Zorica, Petrović, Raisa, Kosec, Duško, Nacka-Aleksić, Mirjana, Jasnić, Nebojša, Leposavić, Gordana, "Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor" in Immunologic Research, 67, no. 2-3 (2019):223-240,
https://doi.org/10.1007/s12026-019-09082-y . .
1
13
6
13

Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine

Petrović, Raisa; Arsenović-Ranin, Nevena; Bufan, Biljana; Živković, Irena; Prijić, Ivana; Stoiljković, Vera; Leposavić, Gordana

(Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia, 2019)

TY  - CONF
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
AU  - Živković, Irena
AU  - Prijić, Ivana
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/692
AB  - Efficacy of the immune response to vaccine depends on genetic background, sex and
age of the recipient. However, mechanisms underlying this phenomenon have not been
elucidated, yet. The study investigated influence of sex and age on serum IgG response
to seasonal trivalent inactivated split influenza vaccine (TIV) in BALB/c and C57BL/6
mice, and mechanisms underlying this response. Total serum IgG responses to
influenza virus type A strains declined with aging, in a strain-specific manner.
Consequently, strain differences (greater IgG responses in BALB/c mice) observed in
young mice (three-month-old) were abrogated in old (eighteen-month-old) ones.
However, irrespective of strain and age, females developed stronger influenza type Aspecific IgG responses than males. Despite age-related decrease in influenza B-specific
serum IgG response, it was comparable between old BALB/c and C57BL/6 mice. The
strain/sex-specific differences in age-related changes in the magnitudes of IgG
responses to TIV correlated with those in number of germinal centre (GC) B
splenocytes. These differences were related to those in B splenocyte and CD4+
splenocyte proliferation in culture upon restimulation with influenza viruses from TIV.
The magnitudes of IgG responses also correlated to T follicular regulatory (Tfr)/T
follicular helper and Tfr/GC B splenocyte ratios across all groups of mice. Aging,
irrespective of influenza virus-specificity, affected serum IgG2a(c)/IgG1 ratios
(reflecting IFN-γ/IL-4 production level ratio) in male BALB/c and female C57BL/6
mice, respectively. Thus, although in young mice of both strains these ratios were
comparable between sexes, in old females they were shifted towards IgG1 when
compared with age-matched males. Consistently, the IFN-γ/IL-4 production level ratios
in splenocyte cultures stimulated with influenza viruses from old females of both strains
were shifted towards IL-4 compared with that in age-matched male cultures. The study
stimulates further research to formulate sex-specific strategies to improve efficacy of
influenza vaccine in elderly.
PB  - Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia
C3  - Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th
T1  - Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine
UR  - https://hdl.handle.net/21.15107/rcub_intor_692
ER  - 
@conference{
author = "Petrović, Raisa and Arsenović-Ranin, Nevena and Bufan, Biljana and Živković, Irena and Prijić, Ivana and Stoiljković, Vera and Leposavić, Gordana",
year = "2019",
abstract = "Efficacy of the immune response to vaccine depends on genetic background, sex and
age of the recipient. However, mechanisms underlying this phenomenon have not been
elucidated, yet. The study investigated influence of sex and age on serum IgG response
to seasonal trivalent inactivated split influenza vaccine (TIV) in BALB/c and C57BL/6
mice, and mechanisms underlying this response. Total serum IgG responses to
influenza virus type A strains declined with aging, in a strain-specific manner.
Consequently, strain differences (greater IgG responses in BALB/c mice) observed in
young mice (three-month-old) were abrogated in old (eighteen-month-old) ones.
However, irrespective of strain and age, females developed stronger influenza type Aspecific IgG responses than males. Despite age-related decrease in influenza B-specific
serum IgG response, it was comparable between old BALB/c and C57BL/6 mice. The
strain/sex-specific differences in age-related changes in the magnitudes of IgG
responses to TIV correlated with those in number of germinal centre (GC) B
splenocytes. These differences were related to those in B splenocyte and CD4+
splenocyte proliferation in culture upon restimulation with influenza viruses from TIV.
The magnitudes of IgG responses also correlated to T follicular regulatory (Tfr)/T
follicular helper and Tfr/GC B splenocyte ratios across all groups of mice. Aging,
irrespective of influenza virus-specificity, affected serum IgG2a(c)/IgG1 ratios
(reflecting IFN-γ/IL-4 production level ratio) in male BALB/c and female C57BL/6
mice, respectively. Thus, although in young mice of both strains these ratios were
comparable between sexes, in old females they were shifted towards IgG1 when
compared with age-matched males. Consistently, the IFN-γ/IL-4 production level ratios
in splenocyte cultures stimulated with influenza viruses from old females of both strains
were shifted towards IL-4 compared with that in age-matched male cultures. The study
stimulates further research to formulate sex-specific strategies to improve efficacy of
influenza vaccine in elderly.",
publisher = "Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia",
journal = "Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th",
title = "Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine",
url = "https://hdl.handle.net/21.15107/rcub_intor_692"
}
Petrović, R., Arsenović-Ranin, N., Bufan, B., Živković, I., Prijić, I., Stoiljković, V.,& Leposavić, G.. (2019). Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine. in Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th
Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia..
https://hdl.handle.net/21.15107/rcub_intor_692
Petrović R, Arsenović-Ranin N, Bufan B, Živković I, Prijić I, Stoiljković V, Leposavić G. Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine. in Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th. 2019;.
https://hdl.handle.net/21.15107/rcub_intor_692 .
Petrović, Raisa, Arsenović-Ranin, Nevena, Bufan, Biljana, Živković, Irena, Prijić, Ivana, Stoiljković, Vera, Leposavić, Gordana, "Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine" in Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th (2019),
https://hdl.handle.net/21.15107/rcub_intor_692 .

Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis

Dimitrijević, Mirjana; Arsenović-Ranin, Nevena; Kosec, Duško; Bufan, Biljana; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Leposavić, Gordana

(Academic Press Inc Elsevier Science, San Diego, 2019)

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/538
AB  - Collagen type II-induced arthritis (CIA) in Dark Agouti rats, a model of rheumatoid arthritis (RA), reproduces sexual dimorphism in the incidence and severity of the human disease. Th17 cells are central in the induction/propagation of autoimmune inflammation in CIA and RA. To assess mechanisms underlying this dimorphism in CIA rats, in lymph nodes draining inflamed joints and adjacent tissues (dLNs) from CIA rats of both sexes Th17/CD25 + Foxp3 + CD4 + T-regulatory cell (Treg) ratio, Th17 cell redifferentiation in functionally distinct subsets and Treg transdifferentiation into IL-17-producing cells (exTregs) were examined. In female rats (developing more severe CIA than their male counterparts) the higher frequency of all Th17 cells (reflecting partly their greater proliferation), followed by the higher frequency of highly pathogenic IFN-gamma/GM-CSF-co-producing cells, but lower frequency of less pathogenic/immunoregulatory IL-10-producing cells among them was found. Additionally, compared with male rats, in female rats the lower frequency of Tregs was observed. Moreover, Tregs from female rats exhibited diminished proliferative and suppressive capacity (judging by PD-1 expression) and enhanced conversion into IL-17-producing cells. Given that TGF-beta concentration was comparable in collagen-type II-stimulated dLN cell cultures from female and male rats, the shift in Th17/Treg ratio followed by augmented Th17 cell redifferentiation into IFN-gamma/GM-CSF-co-producing cells and Treg transdifferentiation into IL-17-producing cells in female rats was associated with increased concentration of IL-6 in female rat dLN cell cultures, and the higher frequency of IL-1 beta- and IL-23-producing cells among their dLN cells. The lower frequency of IL-10-producing B cells, presumably B regulatory cells (Bregs) could also contribute to the shift in Th17/Treg ratio in female rat compared with male rat dLNs. Consistently, the lower expression of IL-35 (the cytokine promoting Treg expansion directly and indirectly, by favoring Breg expansion and conversion into IL-10/IL-35-producing cells) in female rat dLN cells was detected. Thus, the study identified putative cellular and molecular substrates of the sexual dimorphism in the immunopathogenesis and clinical outcome of CIA and suggested mechanisms to be targeted in females to improve control of Th17 response, and consequently clinical outcome of CIA, and possibly RA.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Brain Behavior and Immunity
T1  - Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis
EP  - 214
SP  - 198
VL  - 76
DO  - 10.1016/j.bbi.2018.11.311
ER  - 
@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana",
year = "2019",
abstract = "Collagen type II-induced arthritis (CIA) in Dark Agouti rats, a model of rheumatoid arthritis (RA), reproduces sexual dimorphism in the incidence and severity of the human disease. Th17 cells are central in the induction/propagation of autoimmune inflammation in CIA and RA. To assess mechanisms underlying this dimorphism in CIA rats, in lymph nodes draining inflamed joints and adjacent tissues (dLNs) from CIA rats of both sexes Th17/CD25 + Foxp3 + CD4 + T-regulatory cell (Treg) ratio, Th17 cell redifferentiation in functionally distinct subsets and Treg transdifferentiation into IL-17-producing cells (exTregs) were examined. In female rats (developing more severe CIA than their male counterparts) the higher frequency of all Th17 cells (reflecting partly their greater proliferation), followed by the higher frequency of highly pathogenic IFN-gamma/GM-CSF-co-producing cells, but lower frequency of less pathogenic/immunoregulatory IL-10-producing cells among them was found. Additionally, compared with male rats, in female rats the lower frequency of Tregs was observed. Moreover, Tregs from female rats exhibited diminished proliferative and suppressive capacity (judging by PD-1 expression) and enhanced conversion into IL-17-producing cells. Given that TGF-beta concentration was comparable in collagen-type II-stimulated dLN cell cultures from female and male rats, the shift in Th17/Treg ratio followed by augmented Th17 cell redifferentiation into IFN-gamma/GM-CSF-co-producing cells and Treg transdifferentiation into IL-17-producing cells in female rats was associated with increased concentration of IL-6 in female rat dLN cell cultures, and the higher frequency of IL-1 beta- and IL-23-producing cells among their dLN cells. The lower frequency of IL-10-producing B cells, presumably B regulatory cells (Bregs) could also contribute to the shift in Th17/Treg ratio in female rat compared with male rat dLNs. Consistently, the lower expression of IL-35 (the cytokine promoting Treg expansion directly and indirectly, by favoring Breg expansion and conversion into IL-10/IL-35-producing cells) in female rat dLN cells was detected. Thus, the study identified putative cellular and molecular substrates of the sexual dimorphism in the immunopathogenesis and clinical outcome of CIA and suggested mechanisms to be targeted in females to improve control of Th17 response, and consequently clinical outcome of CIA, and possibly RA.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Brain Behavior and Immunity",
title = "Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis",
pages = "214-198",
volume = "76",
doi = "10.1016/j.bbi.2018.11.311"
}
Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2019). Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis. in Brain Behavior and Immunity
Academic Press Inc Elsevier Science, San Diego., 76, 198-214.
https://doi.org/10.1016/j.bbi.2018.11.311
Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis. in Brain Behavior and Immunity. 2019;76:198-214.
doi:10.1016/j.bbi.2018.11.311 .
Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis" in Brain Behavior and Immunity, 76 (2019):198-214,
https://doi.org/10.1016/j.bbi.2018.11.311 . .
4
18
12
19

Potential impact of early-life probiotic supplementation on peritoneal macrophage function

Blagojević, Veljko; Petrović, Raisa; Ćuruvija, Ivana; Prijić, Ivana; Vujić, Vesna; Stanojević, Stanislava

(Belgrade: Institute for Biological Research "Siniša Stanković", 2019)

TY  - CONF
AU  - Blagojević, Veljko
AU  - Petrović, Raisa
AU  - Ćuruvija, Ivana
AU  - Prijić, Ivana
AU  - Vujić, Vesna
AU  - Stanojević, Stanislava
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/665
AB  - Clinical and animal trials show that early life probiotic consumption provides health benefits in adult life by modulating the immune response. We tested the effects of early life oral consumption of the probiotic Lactobacillus rhamnosus on the function and phenotype of rat peritoneal cavity cells in a model of induced colitis. For the first month of their lives, rats were either fed with an aqueous probiotic bacteria suspension (LB group) or tap water (control group). When the rats grew to 3 months old, we studied the response of their peritoneal macrophages to autologous fecal bacteria stimulation in vitro, both before and after colitis induction (TNBS 40mg/kg of body mass in 50% ethanol). Compared to the controls, the peritoneal cavity cells of the LB group produced less nitric oxide (NO) and had an increased proportion of CD163+ cells. The rats in the LB group have shown milder symptoms of colitis (shorter length of colon under necrosis, less severe submucosal infiltration, lesser degree of colonic wall thickening), along with a diminished increase of peritoneal proinflammatory CCR7+ cells and blunted NO production in response to stimulation by autologous fecal bacteria. Our results may indicate that early oral probiotic administration attenuates macrophage responses to fecal bacteria, which are the primary cause of tissue inflammation and necrosis in chemically induced colitis models, and that this attenuation may be involved in improving the health of colitic rats.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"
PB  - University of Belgrade; Immunological Society of Serbia
C3  - Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - Potential impact of early-life probiotic supplementation on peritoneal macrophage function
SP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_intor_665
ER  - 
@conference{
author = "Blagojević, Veljko and Petrović, Raisa and Ćuruvija, Ivana and Prijić, Ivana and Vujić, Vesna and Stanojević, Stanislava",
year = "2019",
abstract = "Clinical and animal trials show that early life probiotic consumption provides health benefits in adult life by modulating the immune response. We tested the effects of early life oral consumption of the probiotic Lactobacillus rhamnosus on the function and phenotype of rat peritoneal cavity cells in a model of induced colitis. For the first month of their lives, rats were either fed with an aqueous probiotic bacteria suspension (LB group) or tap water (control group). When the rats grew to 3 months old, we studied the response of their peritoneal macrophages to autologous fecal bacteria stimulation in vitro, both before and after colitis induction (TNBS 40mg/kg of body mass in 50% ethanol). Compared to the controls, the peritoneal cavity cells of the LB group produced less nitric oxide (NO) and had an increased proportion of CD163+ cells. The rats in the LB group have shown milder symptoms of colitis (shorter length of colon under necrosis, less severe submucosal infiltration, lesser degree of colonic wall thickening), along with a diminished increase of peritoneal proinflammatory CCR7+ cells and blunted NO production in response to stimulation by autologous fecal bacteria. Our results may indicate that early oral probiotic administration attenuates macrophage responses to fecal bacteria, which are the primary cause of tissue inflammation and necrosis in chemically induced colitis models, and that this attenuation may be involved in improving the health of colitic rats.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade; Immunological Society of Serbia",
journal = "Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "Potential impact of early-life probiotic supplementation on peritoneal macrophage function",
pages = "34",
url = "https://hdl.handle.net/21.15107/rcub_intor_665"
}
Blagojević, V., Petrović, R., Ćuruvija, I., Prijić, I., Vujić, V.,& Stanojević, S.. (2019). Potential impact of early-life probiotic supplementation on peritoneal macrophage function. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"., 34.
https://hdl.handle.net/21.15107/rcub_intor_665
Blagojević V, Petrović R, Ćuruvija I, Prijić I, Vujić V, Stanojević S. Potential impact of early-life probiotic supplementation on peritoneal macrophage function. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2019;:34.
https://hdl.handle.net/21.15107/rcub_intor_665 .
Blagojević, Veljko, Petrović, Raisa, Ćuruvija, Ivana, Prijić, Ivana, Vujić, Vesna, Stanojević, Stanislava, "Potential impact of early-life probiotic supplementation on peritoneal macrophage function" in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia (2019):34,
https://hdl.handle.net/21.15107/rcub_intor_665 .

17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner

Ćuruvija, Ivana; Stanojević, Stanislava; Blagojević, Veljko; Petrović, Raisa; Prijić, Ivana; Vujić, Vesna

(Belgrade: Institute for Biological Research "Siniša Stanković", 2019)

TY  - CONF
AU  - Ćuruvija, Ivana
AU  - Stanojević, Stanislava
AU  - Blagojević, Veljko
AU  - Petrović, Raisa
AU  - Prijić, Ivana
AU  - Vujić, Vesna
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/664
AB  - Aging differently affects the expression of estrogen receptors alpha and beta
(ERα and ERβ) and Toll-like receptors (TLR4) on peritoneal cavity cells of
male and female rats. We explored the involvement of ERα and ERβ in the in
vitro treatment of LPS-stimulated peritoneal macrophages with 17β-estradiol
(which stimulates both receptors) or genistein (which is predominantly an ERβ
agonist) on inflammatory cytokine secretion from young (3 months old) and
middle-aged (16 months old) female and male AO rats. Aging diminished the
proportion of TLR4+ cells and secretion of IL-1β and IL-6 in macrophages
from female rats while the effect on male rat macrophages was opposite. 17βestradiol increased IL-1β secretion by middle-aged females’ macrophages via
ERα, and suppressed it in cells from young females via ERβ. Genistein-induced
decrease of IL-1β in macrophages from all experimental groups was probably
mediated by ERβ. 17β-estradiol augmented IL-6 secretion by cells from all
experimental groups via ERα while genistein diminished it in all females’ and
in middle-aged male rats’ macrophages by activating ERβ. However, genistein
increased IL-6 secretion from macrophages of young male rats via ERα.
Although 17β-estradiol and genistein stimulated secretion of macrophage
inflammatory cytokines via ERα and suppressed it probably via ERβ, their
modulatory actions were determined by aging-induced changes in macrophage
ERs expression and possible ERα / ERβ interactions (Supported by Ministry of
Education, Science and Technological development, Republic of Serbia, Grant
No 175050).
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"
PB  - University of Belgrade; Immunological Society of Serbia
C3  - Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia.
T1  - 17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner
EP  - 132
SP  - 132
UR  - https://hdl.handle.net/21.15107/rcub_intor_664
ER  - 
@conference{
author = "Ćuruvija, Ivana and Stanojević, Stanislava and Blagojević, Veljko and Petrović, Raisa and Prijić, Ivana and Vujić, Vesna",
year = "2019",
abstract = "Aging differently affects the expression of estrogen receptors alpha and beta
(ERα and ERβ) and Toll-like receptors (TLR4) on peritoneal cavity cells of
male and female rats. We explored the involvement of ERα and ERβ in the in
vitro treatment of LPS-stimulated peritoneal macrophages with 17β-estradiol
(which stimulates both receptors) or genistein (which is predominantly an ERβ
agonist) on inflammatory cytokine secretion from young (3 months old) and
middle-aged (16 months old) female and male AO rats. Aging diminished the
proportion of TLR4+ cells and secretion of IL-1β and IL-6 in macrophages
from female rats while the effect on male rat macrophages was opposite. 17βestradiol increased IL-1β secretion by middle-aged females’ macrophages via
ERα, and suppressed it in cells from young females via ERβ. Genistein-induced
decrease of IL-1β in macrophages from all experimental groups was probably
mediated by ERβ. 17β-estradiol augmented IL-6 secretion by cells from all
experimental groups via ERα while genistein diminished it in all females’ and
in middle-aged male rats’ macrophages by activating ERβ. However, genistein
increased IL-6 secretion from macrophages of young male rats via ERα.
Although 17β-estradiol and genistein stimulated secretion of macrophage
inflammatory cytokines via ERα and suppressed it probably via ERβ, their
modulatory actions were determined by aging-induced changes in macrophage
ERs expression and possible ERα / ERβ interactions (Supported by Ministry of
Education, Science and Technological development, Republic of Serbia, Grant
No 175050).",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade; Immunological Society of Serbia",
journal = "Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia.",
title = "17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner",
pages = "132-132",
url = "https://hdl.handle.net/21.15107/rcub_intor_664"
}
Ćuruvija, I., Stanojević, S., Blagojević, V., Petrović, R., Prijić, I.,& Vujić, V.. (2019). 17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia.
Belgrade: Institute for Biological Research "Siniša Stanković"., 132-132.
https://hdl.handle.net/21.15107/rcub_intor_664
Ćuruvija I, Stanojević S, Blagojević V, Petrović R, Prijić I, Vujić V. 17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia.. 2019;:132-132.
https://hdl.handle.net/21.15107/rcub_intor_664 .
Ćuruvija, Ivana, Stanojević, Stanislava, Blagojević, Veljko, Petrović, Raisa, Prijić, Ivana, Vujić, Vesna, "17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner" in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia. (2019):132-132,
https://hdl.handle.net/21.15107/rcub_intor_664 .

Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences

Arsenović-Ranin, Nevena; Petrović, Raisa; Živković, Irena; Bufan, Biljana; Stoiljković, Vera; Leposavić, Gordana

(Springer, New York, 2019)

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Bufan, Biljana
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/534
AB  - The study examined sex-specificities in age-related changes in BALB/c mice IgG antibody responses to immunisation with trivalent inactivated split-virus influenza bulk. Aging diminished the total serum IgG antibody responses to H1N1 and H3N2 and B influenza virus antigens in mice of both sexes, but they remained greater in aged females. This sex difference in aged mice correlated with the greater post-immunisation increase in the frequency of spleen germinal centre (GC) B cells and more favourable T follicular regulatory (Tfr)/GC B cell ratio, as Tfr cells are suggested to control antibody production through suppression of glycolysis. The greater post-immunisation GC B cell response in aged females compared with males correlated with the greater proliferation of B cells and CD4+ cells in splenocyte cultures from aged females restimulated with inactivated split-virus influenza from the bulk. To support the greater post-immunisation increase in the frequency GC B cell in aged females was more favourable Tfr/T follicular helper (Tfh) cell ratio. Additionally, compared with aged males, in age-matched females the greater avidity of serum IgG antibodies was found. However, in aged females IgG2a/IgG1 antibody ratio, reflecting spleen Th1/Th2 cytokine balance, was shifted towards IgG1 when compared with age-matched male mice. This shift was ascribed to a more prominent decline in the titres of functionally important IgG2a antibodies in females with aging. The study suggest that biological sex should be considered as a variable in designing strategies to manipulate with immune outcome of immunisation in aged animals, and possibly, at very long distance, humans.
PB  - Springer, New York
T2  - Biogerontology
T1  - Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences
EP  - 496
IS  - 4
SP  - 475
VL  - 20
DO  - 10.1007/s10522-019-09811-8
ER  - 
@article{
author = "Arsenović-Ranin, Nevena and Petrović, Raisa and Živković, Irena and Bufan, Biljana and Stoiljković, Vera and Leposavić, Gordana",
year = "2019",
abstract = "The study examined sex-specificities in age-related changes in BALB/c mice IgG antibody responses to immunisation with trivalent inactivated split-virus influenza bulk. Aging diminished the total serum IgG antibody responses to H1N1 and H3N2 and B influenza virus antigens in mice of both sexes, but they remained greater in aged females. This sex difference in aged mice correlated with the greater post-immunisation increase in the frequency of spleen germinal centre (GC) B cells and more favourable T follicular regulatory (Tfr)/GC B cell ratio, as Tfr cells are suggested to control antibody production through suppression of glycolysis. The greater post-immunisation GC B cell response in aged females compared with males correlated with the greater proliferation of B cells and CD4+ cells in splenocyte cultures from aged females restimulated with inactivated split-virus influenza from the bulk. To support the greater post-immunisation increase in the frequency GC B cell in aged females was more favourable Tfr/T follicular helper (Tfh) cell ratio. Additionally, compared with aged males, in age-matched females the greater avidity of serum IgG antibodies was found. However, in aged females IgG2a/IgG1 antibody ratio, reflecting spleen Th1/Th2 cytokine balance, was shifted towards IgG1 when compared with age-matched male mice. This shift was ascribed to a more prominent decline in the titres of functionally important IgG2a antibodies in females with aging. The study suggest that biological sex should be considered as a variable in designing strategies to manipulate with immune outcome of immunisation in aged animals, and possibly, at very long distance, humans.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences",
pages = "496-475",
number = "4",
volume = "20",
doi = "10.1007/s10522-019-09811-8"
}
Arsenović-Ranin, N., Petrović, R., Živković, I., Bufan, B., Stoiljković, V.,& Leposavić, G.. (2019). Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences. in Biogerontology
Springer, New York., 20(4), 475-496.
https://doi.org/10.1007/s10522-019-09811-8
Arsenović-Ranin N, Petrović R, Živković I, Bufan B, Stoiljković V, Leposavić G. Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences. in Biogerontology. 2019;20(4):475-496.
doi:10.1007/s10522-019-09811-8 .
Arsenović-Ranin, Nevena, Petrović, Raisa, Živković, Irena, Bufan, Biljana, Stoiljković, Vera, Leposavić, Gordana, "Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences" in Biogerontology, 20, no. 4 (2019):475-496,
https://doi.org/10.1007/s10522-019-09811-8 . .
1
16
11
15

Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation

Nacka-Aleksić, Mirjana; Pilipović, Ivan; Kotur-Stevuljević, Jelena; Petrović, Raisa; Sopta, Jelena; Leposavić, Gordana

(Springer, New York, 2019)

TY  - JOUR
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Kotur-Stevuljević, Jelena
AU  - Petrović, Raisa
AU  - Sopta, Jelena
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/540
AB  - The study investigated mechanisms underlying sex differences in thymic involution in Dark Agouti rats. Adverse effects of aging on thymus were more pronounced in males than in females. Thymi from old males exhibited more prominent: (i) fibro-adipose degeneration which correlated with greater intensity of thymic oxidative stress and enhanced thymic TGF- and IL-6 expression and (ii) decline in thymopoiesis, as suggested by the number of the most mature CD4+CD8-/CD4-CD8+ single positive (SP) TCRhigh thymocytes. The greater accumulation of adipose tissue in old male thymus was linked with greater age-related increase in thymic expression of PPAR and STAT3, a transcription factor regulating the expression of PPAR downstream genes, in male than in female rats. In aged thymi of both sexes the early CD4-CD8- double negative (DN) stage of thymocyte development was affected, so relative accumulation of the least mature CD45RC+CD2- cells followed by decreased frequency of their DN and CD4+CD8+ double positive (DP) TCR- descendants was observed. Additionally, in old males, because of the increased thymic expression of Nur77, a nuclear receptor involved in negative selection, and decreased CD90 (a negative regulator of thymocyte selection threshold) MFI on DP TCRint thymocytes, less efficient positive/more efficient negative selection was found. Moreover, in male rats, thymocyte post-selection differentiation/maturation was skewed towards CD4-CD8+ SP TCRhigh cells compared with age-matched females, reflecting, at least partly, greater IL-15 expression in their thymi. The study indicated mechanisms underlying sex-based differences in age-related thymic changes and consequently necessity of sex-specific approaches in designing strategies to rejuvenate thymus.
PB  - Springer, New York
T2  - Biogerontology
T1  - Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation
EP  - 569
IS  - 4
SP  - 545
VL  - 20
DO  - 10.1007/s10522-019-09816-3
ER  - 
@article{
author = "Nacka-Aleksić, Mirjana and Pilipović, Ivan and Kotur-Stevuljević, Jelena and Petrović, Raisa and Sopta, Jelena and Leposavić, Gordana",
year = "2019",
abstract = "The study investigated mechanisms underlying sex differences in thymic involution in Dark Agouti rats. Adverse effects of aging on thymus were more pronounced in males than in females. Thymi from old males exhibited more prominent: (i) fibro-adipose degeneration which correlated with greater intensity of thymic oxidative stress and enhanced thymic TGF- and IL-6 expression and (ii) decline in thymopoiesis, as suggested by the number of the most mature CD4+CD8-/CD4-CD8+ single positive (SP) TCRhigh thymocytes. The greater accumulation of adipose tissue in old male thymus was linked with greater age-related increase in thymic expression of PPAR and STAT3, a transcription factor regulating the expression of PPAR downstream genes, in male than in female rats. In aged thymi of both sexes the early CD4-CD8- double negative (DN) stage of thymocyte development was affected, so relative accumulation of the least mature CD45RC+CD2- cells followed by decreased frequency of their DN and CD4+CD8+ double positive (DP) TCR- descendants was observed. Additionally, in old males, because of the increased thymic expression of Nur77, a nuclear receptor involved in negative selection, and decreased CD90 (a negative regulator of thymocyte selection threshold) MFI on DP TCRint thymocytes, less efficient positive/more efficient negative selection was found. Moreover, in male rats, thymocyte post-selection differentiation/maturation was skewed towards CD4-CD8+ SP TCRhigh cells compared with age-matched females, reflecting, at least partly, greater IL-15 expression in their thymi. The study indicated mechanisms underlying sex-based differences in age-related thymic changes and consequently necessity of sex-specific approaches in designing strategies to rejuvenate thymus.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation",
pages = "569-545",
number = "4",
volume = "20",
doi = "10.1007/s10522-019-09816-3"
}
Nacka-Aleksić, M., Pilipović, I., Kotur-Stevuljević, J., Petrović, R., Sopta, J.,& Leposavić, G.. (2019). Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation. in Biogerontology
Springer, New York., 20(4), 545-569.
https://doi.org/10.1007/s10522-019-09816-3
Nacka-Aleksić M, Pilipović I, Kotur-Stevuljević J, Petrović R, Sopta J, Leposavić G. Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation. in Biogerontology. 2019;20(4):545-569.
doi:10.1007/s10522-019-09816-3 .
Nacka-Aleksić, Mirjana, Pilipović, Ivan, Kotur-Stevuljević, Jelena, Petrović, Raisa, Sopta, Jelena, Leposavić, Gordana, "Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation" in Biogerontology, 20, no. 4 (2019):545-569,
https://doi.org/10.1007/s10522-019-09816-3 . .
1
13
8
13

Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): lessons from research on rats with distinct age and strain

Đuretić, Jasmina; Pilipović, Ivan; Stojić-Vukanić, Zorica; Leposavić, Gordana

(Termedia Publishing House Ltd, Poznan, 2019)

TY  - JOUR
AU  - Đuretić, Jasmina
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/525
AB  - Natural killer (NK) cells, influencing dendritic cell (DC)-mediated CD4+ lymphocyte priming in draining lymph nodes (dLNs) and controlling spinal cord (SC) infiltration with encephalitogenic CD4+T lymphocytes, modulate EAE (multiple sclerosis model). This study examined their putative contribution to age-related differences in EAE development in Dark Agouti (DA) (exhibiting age-related decrease in EAE susceptibility) and Albino Oxford (AO) (becoming susceptible to EAE with aging) rats. Aging increased NK cell number in dLNs from rats of both strains. In AO rats, but not in DA ones, it also increased the numbers of IFN-gamma-producing NK cells (important for DC activation) and activated/matured DCs, thereby increasing activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated CD25+Foxp3-CD4+ cell number. Aging in DA rats diminished activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated Foxp3-CD4+ cell number. However, MBP-stimulated CD4+ cell proliferation did not differ in dLN cell cultures from young and aged AO rats (as more favorable activated/matured DC/Foxp3-CD4+ cell ratio was abrogated by lower intrinsic CD4+ cell proliferative capacity and a greater regulatory CD25+Foxp3+CD4+ lymphocyte frequency), but was lower in those from aged compared with young DA rats. At SC level, aging shifted Foxp3-CD4+/cytotoxic CX3CR1+ NK cell ratio towards the former in AO rats, so it was less favorable in aged AO rats exhibiting prolonged neurological deficit compared with their DA counterparts. The study showed strain and age differences in number of IFN-gamma-producing NK cells in EAE rat dLNs, and suggested that their pathogenetic relevance depends on frequency and/or activity of other cells involved in CD4+ T cell (auto)immune response.
PB  - Termedia Publishing House Ltd, Poznan
T2  - Central European Journal of Immunology
T1  - Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): lessons from research on rats with distinct age and strain
EP  - 356
IS  - 4
SP  - 337
VL  - 44
DO  - 10.5114/ceji.2019.92777
ER  - 
@article{
author = "Đuretić, Jasmina and Pilipović, Ivan and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2019",
abstract = "Natural killer (NK) cells, influencing dendritic cell (DC)-mediated CD4+ lymphocyte priming in draining lymph nodes (dLNs) and controlling spinal cord (SC) infiltration with encephalitogenic CD4+T lymphocytes, modulate EAE (multiple sclerosis model). This study examined their putative contribution to age-related differences in EAE development in Dark Agouti (DA) (exhibiting age-related decrease in EAE susceptibility) and Albino Oxford (AO) (becoming susceptible to EAE with aging) rats. Aging increased NK cell number in dLNs from rats of both strains. In AO rats, but not in DA ones, it also increased the numbers of IFN-gamma-producing NK cells (important for DC activation) and activated/matured DCs, thereby increasing activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated CD25+Foxp3-CD4+ cell number. Aging in DA rats diminished activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated Foxp3-CD4+ cell number. However, MBP-stimulated CD4+ cell proliferation did not differ in dLN cell cultures from young and aged AO rats (as more favorable activated/matured DC/Foxp3-CD4+ cell ratio was abrogated by lower intrinsic CD4+ cell proliferative capacity and a greater regulatory CD25+Foxp3+CD4+ lymphocyte frequency), but was lower in those from aged compared with young DA rats. At SC level, aging shifted Foxp3-CD4+/cytotoxic CX3CR1+ NK cell ratio towards the former in AO rats, so it was less favorable in aged AO rats exhibiting prolonged neurological deficit compared with their DA counterparts. The study showed strain and age differences in number of IFN-gamma-producing NK cells in EAE rat dLNs, and suggested that their pathogenetic relevance depends on frequency and/or activity of other cells involved in CD4+ T cell (auto)immune response.",
publisher = "Termedia Publishing House Ltd, Poznan",
journal = "Central European Journal of Immunology",
title = "Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): lessons from research on rats with distinct age and strain",
pages = "356-337",
number = "4",
volume = "44",
doi = "10.5114/ceji.2019.92777"
}
Đuretić, J., Pilipović, I., Stojić-Vukanić, Z.,& Leposavić, G.. (2019). Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): lessons from research on rats with distinct age and strain. in Central European Journal of Immunology
Termedia Publishing House Ltd, Poznan., 44(4), 337-356.
https://doi.org/10.5114/ceji.2019.92777
Đuretić J, Pilipović I, Stojić-Vukanić Z, Leposavić G. Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): lessons from research on rats with distinct age and strain. in Central European Journal of Immunology. 2019;44(4):337-356.
doi:10.5114/ceji.2019.92777 .
Đuretić, Jasmina, Pilipović, Ivan, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): lessons from research on rats with distinct age and strain" in Central European Journal of Immunology, 44, no. 4 (2019):337-356,
https://doi.org/10.5114/ceji.2019.92777 . .
3
2
3

Noradrenaline synthesized locally in draining lymph node cells modulates CD4+ T-cell development in rat EAE model: a role for a1-adrenoceptor

Pilipović, Ivan; Vujnović, I.; Petrović, Raisa; Kosec, Duško; Stojić-Vukanić, Z.; Leposavić, Gordana

(2018)

TY  - CONF
AU  - Pilipović, Ivan
AU  - Vujnović, I.
AU  - Petrović, Raisa
AU  - Kosec, Duško
AU  - Stojić-Vukanić, Z.
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/853
AB  - Introduction: It has been suggested that: i) noradrenaline synthesis in ,,adrenergic“ immune cells changes during development of EAE and multiple sclerosis and ii) noradrenaline influences EAE development through a1−adrenoceptor. To elucidate mechanisms standing behind this phenomenon, a1−adrenoceptor−mediated influence of draining lymph node (dLN) cell−derived noradrenaline on CD4+ T−cell response in dLNs from Dark Agouti rats of both sexes immunized for EAE was examined. Methods: Cells recovered from dLNs on 7th day post−immunization were examined for noradrenaline synthesis/content and a1B−adrenoceptor expression using HPLC and/or flow cytometry. Additionally, effects of prazosin (a1- AR blocker) on CD4+ T−cell proliferation, the frequency of IL−17+ CD4+ T−cells and regulatory (Foxp3+CD25+) CD4+ T−cells (Tregs), activational/maturational molecule expression on antigen presenting cells (APCs) and their cytokine profile in dLN cell culture were examined using flow cytometry and/or qRT−PCR/ELISA. Results: Irrespective of sex, conventional CD4+ T−cells and Tregs, and APCs from rat dLNs synthesized noradrenaline, while only Tregs and APCs expressed a1B-adrenoceptor.
In myelin basic protein−stimulated dLN cell cultures from rats of both sexes prazosin increased Treg frequency and Foxp3 expression, but diminished co−stimulatory CD80 and CD86
molecule expression on APCs, thereby reducing CD4+ cell proliferation.
C3  - Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands
T1  - Noradrenaline synthesized locally in draining lymph node cells modulates CD4+ T-cell development in rat EAE model: a role for a1-adrenoceptor
SP  - P.A5.06.15
UR  - https://hdl.handle.net/21.15107/rcub_intor_853
ER  - 
@conference{
author = "Pilipović, Ivan and Vujnović, I. and Petrović, Raisa and Kosec, Duško and Stojić-Vukanić, Z. and Leposavić, Gordana",
year = "2018",
abstract = "Introduction: It has been suggested that: i) noradrenaline synthesis in ,,adrenergic“ immune cells changes during development of EAE and multiple sclerosis and ii) noradrenaline influences EAE development through a1−adrenoceptor. To elucidate mechanisms standing behind this phenomenon, a1−adrenoceptor−mediated influence of draining lymph node (dLN) cell−derived noradrenaline on CD4+ T−cell response in dLNs from Dark Agouti rats of both sexes immunized for EAE was examined. Methods: Cells recovered from dLNs on 7th day post−immunization were examined for noradrenaline synthesis/content and a1B−adrenoceptor expression using HPLC and/or flow cytometry. Additionally, effects of prazosin (a1- AR blocker) on CD4+ T−cell proliferation, the frequency of IL−17+ CD4+ T−cells and regulatory (Foxp3+CD25+) CD4+ T−cells (Tregs), activational/maturational molecule expression on antigen presenting cells (APCs) and their cytokine profile in dLN cell culture were examined using flow cytometry and/or qRT−PCR/ELISA. Results: Irrespective of sex, conventional CD4+ T−cells and Tregs, and APCs from rat dLNs synthesized noradrenaline, while only Tregs and APCs expressed a1B-adrenoceptor.
In myelin basic protein−stimulated dLN cell cultures from rats of both sexes prazosin increased Treg frequency and Foxp3 expression, but diminished co−stimulatory CD80 and CD86
molecule expression on APCs, thereby reducing CD4+ cell proliferation.",
journal = "Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands",
title = "Noradrenaline synthesized locally in draining lymph node cells modulates CD4+ T-cell development in rat EAE model: a role for a1-adrenoceptor",
pages = "P.A5.06.15",
url = "https://hdl.handle.net/21.15107/rcub_intor_853"
}
Pilipović, I., Vujnović, I., Petrović, R., Kosec, D., Stojić-Vukanić, Z.,& Leposavić, G.. (2018). Noradrenaline synthesized locally in draining lymph node cells modulates CD4+ T-cell development in rat EAE model: a role for a1-adrenoceptor. in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands, P.A5.06.15.
https://hdl.handle.net/21.15107/rcub_intor_853
Pilipović I, Vujnović I, Petrović R, Kosec D, Stojić-Vukanić Z, Leposavić G. Noradrenaline synthesized locally in draining lymph node cells modulates CD4+ T-cell development in rat EAE model: a role for a1-adrenoceptor. in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands. 2018;:P.A5.06.15.
https://hdl.handle.net/21.15107/rcub_intor_853 .
Pilipović, Ivan, Vujnović, I., Petrović, Raisa, Kosec, Duško, Stojić-Vukanić, Z., Leposavić, Gordana, "Noradrenaline synthesized locally in draining lymph node cells modulates CD4+ T-cell development in rat EAE model: a role for a1-adrenoceptor" in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands (2018):P.A5.06.15,
https://hdl.handle.net/21.15107/rcub_intor_853 .

Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE

Nacka-Aleksić, M.; Stojanović, M.; Pilipović, Ivan; Kosec, Duško; Leposavić, Gordana

(2018)

TY  - CONF
AU  - Nacka-Aleksić, M.
AU  - Stojanović, M.
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/851
AB  - Introduction: It is suggested that impaired thymopoiesis in autoimmune diseases contributes to their perpetuation. To prove this hypothesis, influence of immunization for EAE on thymopoiesis and the putative thymic−dependent changes in the periphery were examined in susceptible (Dark Agouti, DA) and resistant (Albino Oxford, AO) rats. Methods: On the 13th day post−immunization, expression of differentiation/maturation markers of conventional T cells and regulatory CD4+Foxp3+CD25+ cells (nTregs) on thymocytes, their apoptosis and proliferation, frequency of recent thymic emigrants (RTEs) and CD28null cells in CD4+ and CD8+ peripheral blood lymphocytes (PBLs), and thymic expression and circulating levels of cytokines influencing thymus/thymopoiesis were investigated. Results: In rats of both strains increase in proinflammatory−cytokine circulating levels followed by thymic atrophy and changes at multiple thymocyte developmental points, leading to decreased number of the most mature CD4+ and CD8+ TCRaβhi thymocytes and frequency of RTEs among PBLs (as in chronobiological aging), was found. This was more prominent in DA rats. Consistently, compared with AO rats, in DA rats were found higher frequencies
of cytolitic CD28null cells (contributing to target tissue damage) among CD4+ PBLs and cytolitic granzyme B+ CD4+ T cells in spinal cord. Additionally, compared with non−immunized controls, DA rats exhibited greater decline in thymic nTreg generation (reflecting diminished thymic IL−7, IL−2 and IL−15 expression) than AO ones. Conclusions: The study suggests that differences in thymopoiesis, and consequently nTreg generation and CD4+CD28null cell frequency in the periphery, contribute to strain differences in EAE clinical presentation.
C3  - Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands
T1  - Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE
SP  - P.A2.03.06
UR  - https://hdl.handle.net/21.15107/rcub_intor_851
ER  - 
@conference{
author = "Nacka-Aleksić, M. and Stojanović, M. and Pilipović, Ivan and Kosec, Duško and Leposavić, Gordana",
year = "2018",
abstract = "Introduction: It is suggested that impaired thymopoiesis in autoimmune diseases contributes to their perpetuation. To prove this hypothesis, influence of immunization for EAE on thymopoiesis and the putative thymic−dependent changes in the periphery were examined in susceptible (Dark Agouti, DA) and resistant (Albino Oxford, AO) rats. Methods: On the 13th day post−immunization, expression of differentiation/maturation markers of conventional T cells and regulatory CD4+Foxp3+CD25+ cells (nTregs) on thymocytes, their apoptosis and proliferation, frequency of recent thymic emigrants (RTEs) and CD28null cells in CD4+ and CD8+ peripheral blood lymphocytes (PBLs), and thymic expression and circulating levels of cytokines influencing thymus/thymopoiesis were investigated. Results: In rats of both strains increase in proinflammatory−cytokine circulating levels followed by thymic atrophy and changes at multiple thymocyte developmental points, leading to decreased number of the most mature CD4+ and CD8+ TCRaβhi thymocytes and frequency of RTEs among PBLs (as in chronobiological aging), was found. This was more prominent in DA rats. Consistently, compared with AO rats, in DA rats were found higher frequencies
of cytolitic CD28null cells (contributing to target tissue damage) among CD4+ PBLs and cytolitic granzyme B+ CD4+ T cells in spinal cord. Additionally, compared with non−immunized controls, DA rats exhibited greater decline in thymic nTreg generation (reflecting diminished thymic IL−7, IL−2 and IL−15 expression) than AO ones. Conclusions: The study suggests that differences in thymopoiesis, and consequently nTreg generation and CD4+CD28null cell frequency in the periphery, contribute to strain differences in EAE clinical presentation.",
journal = "Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands",
title = "Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE",
pages = "P.A2.03.06",
url = "https://hdl.handle.net/21.15107/rcub_intor_851"
}
Nacka-Aleksić, M., Stojanović, M., Pilipović, I., Kosec, D.,& Leposavić, G.. (2018). Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE. in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands, P.A2.03.06.
https://hdl.handle.net/21.15107/rcub_intor_851
Nacka-Aleksić M, Stojanović M, Pilipović I, Kosec D, Leposavić G. Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE. in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands. 2018;:P.A2.03.06.
https://hdl.handle.net/21.15107/rcub_intor_851 .
Nacka-Aleksić, M., Stojanović, M., Pilipović, Ivan, Kosec, Duško, Leposavić, Gordana, "Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE" in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands (2018):P.A2.03.06,
https://hdl.handle.net/21.15107/rcub_intor_851 .

Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis

Bufan, B.; Arsenović-Ranin, N.; Dimitrijević, M.; Nacka-Aleksić, M.; Kosec, Duško; Pilipović, Ivan; Stojanović, M.; Leposavić, Gordana

(2018)

TY  - CONF
AU  - Bufan, B.
AU  - Arsenović-Ranin, N.
AU  - Dimitrijević, M.
AU  - Nacka-Aleksić, M.
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Stojanović, M.
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/850
AB  - Introduction: Considering sex bias in rheumatoid arthritis prevalence, influence of biological sex on the disease development in Dark Agouti rat collagen II (CII)−induced arthritis (CIA) model of the human disease was examined. Methods: Sex bias in CD4+ T cell responses in inguinal (draining the site of immunization in preclinical CIA) and popliteal (draining inflamed joints at the peak of CIA) lymph nodes (LNs) and mechanisms controlling their development were examined using flow cytometry and/or ELISA/qRT−PCR. Results: In both inguinal and popliteal LNs greater number of CD4+CD25+Foxp3− cells, presumably activated effector T cells, was found in females compared with males, and they exhibited greater CII−specific proliferation. Consistently, more IL−17+, IFN−γ+ and IL−17+IFN−γ+ T cells were retrieved from both inguinal and popliteal female rat LNs. Moreover, more GM−CSF+ and IL−17+IFN−γ+GM−CSF+ T cells were retrieved from female compared with male rat popliteal LNs. On the other hand, lower frequency of PD−1+ cells among CD4+CD25+Foxp3+ regulatory T cells (Tregs) from female popliteal and inguinal LNs suggested lower suppressive capacity of their Tregs. Additionally, from female rat popliteal LNs fewer Tregs were recovered. Furthermore, the number of regulatory LN B10 cells was lower in females. Moreover, compared with males, in females was shifted LN INF−γ+/IL−4+ T−cell ratio towards the former, and accordingly serum CII−specific IgG2a/IgG1 antibody ratio was shifted towards pathogenic IgG2a antibodies. Conclusion: The study suggests that a less efficient control of (auto)immune Th1/Th17 cell responses during CIA development contributes to sex bias in the susceptibility to CIA.
C3  - 5th European Congress of Immunology, Septembar 2-5, Abstract Book
T1  - Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis
SP  - P.C1.01.02
UR  - https://hdl.handle.net/21.15107/rcub_intor_850
ER  - 
@conference{
author = "Bufan, B. and Arsenović-Ranin, N. and Dimitrijević, M. and Nacka-Aleksić, M. and Kosec, Duško and Pilipović, Ivan and Stojanović, M. and Leposavić, Gordana",
year = "2018",
abstract = "Introduction: Considering sex bias in rheumatoid arthritis prevalence, influence of biological sex on the disease development in Dark Agouti rat collagen II (CII)−induced arthritis (CIA) model of the human disease was examined. Methods: Sex bias in CD4+ T cell responses in inguinal (draining the site of immunization in preclinical CIA) and popliteal (draining inflamed joints at the peak of CIA) lymph nodes (LNs) and mechanisms controlling their development were examined using flow cytometry and/or ELISA/qRT−PCR. Results: In both inguinal and popliteal LNs greater number of CD4+CD25+Foxp3− cells, presumably activated effector T cells, was found in females compared with males, and they exhibited greater CII−specific proliferation. Consistently, more IL−17+, IFN−γ+ and IL−17+IFN−γ+ T cells were retrieved from both inguinal and popliteal female rat LNs. Moreover, more GM−CSF+ and IL−17+IFN−γ+GM−CSF+ T cells were retrieved from female compared with male rat popliteal LNs. On the other hand, lower frequency of PD−1+ cells among CD4+CD25+Foxp3+ regulatory T cells (Tregs) from female popliteal and inguinal LNs suggested lower suppressive capacity of their Tregs. Additionally, from female rat popliteal LNs fewer Tregs were recovered. Furthermore, the number of regulatory LN B10 cells was lower in females. Moreover, compared with males, in females was shifted LN INF−γ+/IL−4+ T−cell ratio towards the former, and accordingly serum CII−specific IgG2a/IgG1 antibody ratio was shifted towards pathogenic IgG2a antibodies. Conclusion: The study suggests that a less efficient control of (auto)immune Th1/Th17 cell responses during CIA development contributes to sex bias in the susceptibility to CIA.",
journal = "5th European Congress of Immunology, Septembar 2-5, Abstract Book",
title = "Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis",
pages = "P.C1.01.02",
url = "https://hdl.handle.net/21.15107/rcub_intor_850"
}
Bufan, B., Arsenović-Ranin, N., Dimitrijević, M., Nacka-Aleksić, M., Kosec, D., Pilipović, I., Stojanović, M.,& Leposavić, G.. (2018). Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis. in 5th European Congress of Immunology, Septembar 2-5, Abstract Book, P.C1.01.02.
https://hdl.handle.net/21.15107/rcub_intor_850
Bufan B, Arsenović-Ranin N, Dimitrijević M, Nacka-Aleksić M, Kosec D, Pilipović I, Stojanović M, Leposavić G. Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis. in 5th European Congress of Immunology, Septembar 2-5, Abstract Book. 2018;:P.C1.01.02.
https://hdl.handle.net/21.15107/rcub_intor_850 .
Bufan, B., Arsenović-Ranin, N., Dimitrijević, M., Nacka-Aleksić, M., Kosec, Duško, Pilipović, Ivan, Stojanović, M., Leposavić, Gordana, "Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis" in 5th European Congress of Immunology, Septembar 2-5, Abstract Book (2018):P.C1.01.02,
https://hdl.handle.net/21.15107/rcub_intor_850 .

Propranolol influences EAE development by impairing antigen presenting cell migration into the draining lymph nodes

Vujinović, I.; Pilipović, Ivan; Petrović, R.; Stojić−Vukanić, Z.; Arsenović−Ranin, N.; Leposavić, Gordana

(2018)

TY  - CONF
AU  - Vujinović, I.
AU  - Pilipović, Ivan
AU  - Petrović, R.
AU  - Stojić−Vukanić, Z.
AU  - Arsenović−Ranin, N.
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/852
AB  - Introduction: Catecholamines are implicated in development of multiple sclerosis and EAE in Dark Agouti (DA) rats. To enlighten their β−adrenoceptor−mediated immunomodulatory action, DA rats of both sexes immunized for EAE were subjected to seven−day−long treatment with propranolol (β−adrenoceptor blocker) starting at the day of immunization.
Methods: The migration of antigen presenting cells (APCs) into the draining lymph nodes (dLNs) was examined using CFSE−based assay. Frequency of activated CD4+ T cells, their proliferation and frequency of IL−17−producing CD4+ T (Th17) cells in dLNs, and their infiltration into spinal cord, were analyzed using flow cytometry. Propranolol effects on CD4+ cell proliferation and Th17 cell polarization, and IL−2 and Th17 polarizing cytokine and chemokine expression in dLNs/ dLN cell cultures were examined using flow cytometry and ELISA/qRT−PCR. Results: Irrespective of sex, propranolol reduced the incidence and postponed clinical EAE onset by impairing migration of antigen−carrying APCs into the dLNs (due to diminished dLN CCL19/21 expression). Consequently, propranolol diminished CD4+ T−cell activation/proliferation, and Th17 cell number in dLNs and spinal cord. To corroborate these findings, propranolol exerted stimulatory effects on CD4+ cell proliferation (through stimulation of IL−2 secretion) and Th17 cell differentiation (reflecting enhanced Th17 polarizing cytokine production) in dLN cell cultures. Conclusions: Irrespective of sex, the stimulatory effects of propranolol on dLN CD4+ T lymphocyte proliferation and activated/ matured APC Th17 polarizing capacity were insufficient to overcome its inhibitory influence on APC migration, so propranolol impaired Th17 generation in dLNs of EAE rats, and postponed EAE development.
C3  - Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands
T1  - Propranolol influences EAE development by impairing antigen presenting cell migration into the draining lymph nodes
SP  - P.A5.06.07
UR  - https://hdl.handle.net/21.15107/rcub_intor_852
ER  - 
@conference{
author = "Vujinović, I. and Pilipović, Ivan and Petrović, R. and Stojić−Vukanić, Z. and Arsenović−Ranin, N. and Leposavić, Gordana",
year = "2018",
abstract = "Introduction: Catecholamines are implicated in development of multiple sclerosis and EAE in Dark Agouti (DA) rats. To enlighten their β−adrenoceptor−mediated immunomodulatory action, DA rats of both sexes immunized for EAE were subjected to seven−day−long treatment with propranolol (β−adrenoceptor blocker) starting at the day of immunization.
Methods: The migration of antigen presenting cells (APCs) into the draining lymph nodes (dLNs) was examined using CFSE−based assay. Frequency of activated CD4+ T cells, their proliferation and frequency of IL−17−producing CD4+ T (Th17) cells in dLNs, and their infiltration into spinal cord, were analyzed using flow cytometry. Propranolol effects on CD4+ cell proliferation and Th17 cell polarization, and IL−2 and Th17 polarizing cytokine and chemokine expression in dLNs/ dLN cell cultures were examined using flow cytometry and ELISA/qRT−PCR. Results: Irrespective of sex, propranolol reduced the incidence and postponed clinical EAE onset by impairing migration of antigen−carrying APCs into the dLNs (due to diminished dLN CCL19/21 expression). Consequently, propranolol diminished CD4+ T−cell activation/proliferation, and Th17 cell number in dLNs and spinal cord. To corroborate these findings, propranolol exerted stimulatory effects on CD4+ cell proliferation (through stimulation of IL−2 secretion) and Th17 cell differentiation (reflecting enhanced Th17 polarizing cytokine production) in dLN cell cultures. Conclusions: Irrespective of sex, the stimulatory effects of propranolol on dLN CD4+ T lymphocyte proliferation and activated/ matured APC Th17 polarizing capacity were insufficient to overcome its inhibitory influence on APC migration, so propranolol impaired Th17 generation in dLNs of EAE rats, and postponed EAE development.",
journal = "Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands",
title = "Propranolol influences EAE development by impairing antigen presenting cell migration into the draining lymph nodes",
pages = "P.A5.06.07",
url = "https://hdl.handle.net/21.15107/rcub_intor_852"
}
Vujinović, I., Pilipović, I., Petrović, R., Stojić−Vukanić, Z., Arsenović−Ranin, N.,& Leposavić, G.. (2018). Propranolol influences EAE development by impairing antigen presenting cell migration into the draining lymph nodes. in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands, P.A5.06.07.
https://hdl.handle.net/21.15107/rcub_intor_852
Vujinović I, Pilipović I, Petrović R, Stojić−Vukanić Z, Arsenović−Ranin N, Leposavić G. Propranolol influences EAE development by impairing antigen presenting cell migration into the draining lymph nodes. in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands. 2018;:P.A5.06.07.
https://hdl.handle.net/21.15107/rcub_intor_852 .
Vujinović, I., Pilipović, Ivan, Petrović, R., Stojić−Vukanić, Z., Arsenović−Ranin, N., Leposavić, Gordana, "Propranolol influences EAE development by impairing antigen presenting cell migration into the draining lymph nodes" in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands (2018):P.A5.06.07,
https://hdl.handle.net/21.15107/rcub_intor_852 .

Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action

Stojić-Vukanić, Zorica; Kotur-Stevuljević, Jelena; Nacka-Aleksić, Mirjana; Kosec, Duško; Vujnović, Ivana; Pilipović, Ivan; Dimitrijević, Mirjana; Leposavić, Gordana

(Springer, New York, 2018)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Kotur-Stevuljević, Jelena
AU  - Nacka-Aleksić, Mirjana
AU  - Kosec, Duško
AU  - Vujnović, Ivana
AU  - Pilipović, Ivan
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/518
AB  - In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage.
PB  - Springer, New York
T2  - Molecular Neurobiology
T1  - Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action
EP  - 3774
IS  - 5
SP  - 3755
VL  - 55
DO  - 10.1007/s12035-017-0595-2
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Kotur-Stevuljević, Jelena and Nacka-Aleksić, Mirjana and Kosec, Duško and Vujnović, Ivana and Pilipović, Ivan and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2018",
abstract = "In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage.",
publisher = "Springer, New York",
journal = "Molecular Neurobiology",
title = "Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action",
pages = "3774-3755",
number = "5",
volume = "55",
doi = "10.1007/s12035-017-0595-2"
}
Stojić-Vukanić, Z., Kotur-Stevuljević, J., Nacka-Aleksić, M., Kosec, D., Vujnović, I., Pilipović, I., Dimitrijević, M.,& Leposavić, G.. (2018). Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action. in Molecular Neurobiology
Springer, New York., 55(5), 3755-3774.
https://doi.org/10.1007/s12035-017-0595-2
Stojić-Vukanić Z, Kotur-Stevuljević J, Nacka-Aleksić M, Kosec D, Vujnović I, Pilipović I, Dimitrijević M, Leposavić G. Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action. in Molecular Neurobiology. 2018;55(5):3755-3774.
doi:10.1007/s12035-017-0595-2 .
Stojić-Vukanić, Zorica, Kotur-Stevuljević, Jelena, Nacka-Aleksić, Mirjana, Kosec, Duško, Vujnović, Ivana, Pilipović, Ivan, Dimitrijević, Mirjana, Leposavić, Gordana, "Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action" in Molecular Neurobiology, 55, no. 5 (2018):3755-3774,
https://doi.org/10.1007/s12035-017-0595-2 . .
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