Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.

<h4>Objective</h4>Immune imbalance between regulatory T (Treg) and Th17 cells is a characteristic of systemic sclerosis (SSc). The functional heterogeneity among Treg can be elucidated by separating Treg into different subsets based on the expression of FoxP3 and CD45RA. The aim of this...

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Autores principales:	Xinjuan Liu, Na Gao, Mengtao Li, Dong Xu, Yong Hou, Qian Wang, Guohua Zhang, Qiuning Sun, Henghui Zhang, Xiaofeng Zeng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9396dc82af424d4abcf3cd520af680b3
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spelling	oai:doaj.org-article:9396dc82af424d4abcf3cd520af680b32021-11-18T07:42:24ZElevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.1932-620310.1371/journal.pone.0064531https://doaj.org/article/9396dc82af424d4abcf3cd520af680b32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23776439/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>Immune imbalance between regulatory T (Treg) and Th17 cells is a characteristic of systemic sclerosis (SSc). The functional heterogeneity among Treg can be elucidated by separating Treg into different subsets based on the expression of FoxP3 and CD45RA. The aim of this study was to investigate the role of Treg subsets in the immune imbalance in naïve SSc.<h4>Methods</h4>Peripheral blood mononuclear cells (PBMCs) of 31 SSc patients and 33 healthy controls were analyzed for the expression of CD4, CD25, CD45RA, CTLA-4, FoxP3, and IL-17 using flow cytometry. Treg immunesuppression capacity was measured in co-culture experiments. The expression of FoxP3, CTLA-4, IL-17A, and RORC mRNA was measured by real-time PCR.<h4>Results</h4>The frequency of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly elevated in patients with SSc (3.62±1.14 vs 1.97±0.75, p<0.001) with diminished immunosuppression capacity. In SSc, the proportion of FoxP3(high)CD45RA(-) activated Treg cells (aTreg) was decreased, the proportion of FoxP3(low)CD45RA(-) T cells was increased, and the proportion of FoxP3(low)CD45RA(+) resting Treg cells (rTreg) was decreased. The immune suppression capacity of aTreg and rTreg was diminished, while FoxP3(low)CD45RA(-) T cells exhibited a lack of suppression capacity. The immune dysfunction of aTreg was accompanied by the abnormal expression of CTLA-4. Th17 cell numbers were elevated in SSc, FoxP3(low)CD45RA(-) T cells produced IL-17, confirming their Th17 potential, which was consistent with the elevated levels of FoxP3(+)IL-17(+) cells in SSc.<h4>Conclusion</h4>A decrease in aTreg levels, along with functional deficiency, and an increase in the proportion of FoxP3(low)CD45RA(-) T cells, was the reason for the increase in dysfunctional Treg in SSc patients, potentially causing the immune imbalance between Treg and Th17 cells.Xinjuan LiuNa GaoMengtao LiDong XuYong HouQian WangGuohua ZhangQiuning SunHenghui ZhangXiaofeng ZengPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e64531 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xinjuan Liu Na Gao Mengtao Li Dong Xu Yong Hou Qian Wang Guohua Zhang Qiuning Sun Henghui Zhang Xiaofeng Zeng Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.
description	<h4>Objective</h4>Immune imbalance between regulatory T (Treg) and Th17 cells is a characteristic of systemic sclerosis (SSc). The functional heterogeneity among Treg can be elucidated by separating Treg into different subsets based on the expression of FoxP3 and CD45RA. The aim of this study was to investigate the role of Treg subsets in the immune imbalance in naïve SSc.<h4>Methods</h4>Peripheral blood mononuclear cells (PBMCs) of 31 SSc patients and 33 healthy controls were analyzed for the expression of CD4, CD25, CD45RA, CTLA-4, FoxP3, and IL-17 using flow cytometry. Treg immunesuppression capacity was measured in co-culture experiments. The expression of FoxP3, CTLA-4, IL-17A, and RORC mRNA was measured by real-time PCR.<h4>Results</h4>The frequency of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly elevated in patients with SSc (3.62±1.14 vs 1.97±0.75, p<0.001) with diminished immunosuppression capacity. In SSc, the proportion of FoxP3(high)CD45RA(-) activated Treg cells (aTreg) was decreased, the proportion of FoxP3(low)CD45RA(-) T cells was increased, and the proportion of FoxP3(low)CD45RA(+) resting Treg cells (rTreg) was decreased. The immune suppression capacity of aTreg and rTreg was diminished, while FoxP3(low)CD45RA(-) T cells exhibited a lack of suppression capacity. The immune dysfunction of aTreg was accompanied by the abnormal expression of CTLA-4. Th17 cell numbers were elevated in SSc, FoxP3(low)CD45RA(-) T cells produced IL-17, confirming their Th17 potential, which was consistent with the elevated levels of FoxP3(+)IL-17(+) cells in SSc.<h4>Conclusion</h4>A decrease in aTreg levels, along with functional deficiency, and an increase in the proportion of FoxP3(low)CD45RA(-) T cells, was the reason for the increase in dysfunctional Treg in SSc patients, potentially causing the immune imbalance between Treg and Th17 cells.
format	article
author	Xinjuan Liu Na Gao Mengtao Li Dong Xu Yong Hou Qian Wang Guohua Zhang Qiuning Sun Henghui Zhang Xiaofeng Zeng
author_facet	Xinjuan Liu Na Gao Mengtao Li Dong Xu Yong Hou Qian Wang Guohua Zhang Qiuning Sun Henghui Zhang Xiaofeng Zeng
author_sort	Xinjuan Liu
title	Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.
title_short	Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.
title_full	Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.
title_fullStr	Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.
title_full_unstemmed	Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.
title_sort	elevated levels of cd4(+)cd25(+)foxp3(+) t cells in systemic sclerosis patients contribute to the secretion of il-17 and immunosuppression dysfunction.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9396dc82af424d4abcf3cd520af680b3
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Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.

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