Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor
Само за регистроване кориснике
2019
Аутори
Pilipović, IvanVujnović, Ivana
Stojić-Vukanić, Zorica
Petrović, Raisa
Kosec, Duško
Nacka-Aleksić, Mirjana
Jasnić, Nebojša
Leposavić, Gordana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 cel...l 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.
Кључне речи:
Noradrenaline / alpha(1)-Adrenoceptor / EAE / Tregs / Th17 / CD4+lymphocyte proliferationИзвор:
Immunologic Research, 2019, 67, 2-3, 223-240Издавач:
- Humana Press Inc, Totowa
Финансирање / пројекти:
DOI: 10.1007/s12026-019-09082-y
ISSN: 0257-277X
PubMed: 31396845
WoS: 000484525000008
Scopus: 2-s2.0-85070290853
Институција/група
TorlakTY - 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 . .