Sexual dimorphism in thymic senescence
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2019
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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.
Izvor:
Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019, 2019, 85-85Izdavač:
- Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade
- Immunological Society of Serbia
Finansiranje / projekti:
- Plastičnost imunskog sistema tokom starenja: imunomodulatorni potencijal estrogena (RS-MESTD-Basic Research (BR or ON)-175050)
Institucija/grupa
TorlakTY - 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 .