Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction.
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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DOI：
10.1371/journal.pone.0064531
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zeng X
中科院分区：
文献类型：
--
作者：
Liu X;Gao N;Li M;Xu D;Hou Y;Wang Q;Zhang G;Sun Q;Zhang H;Zeng X
调节性T（Treg）和Th 17细胞之间的免疫失衡是系统性硬化症（SSc）的特征。Treg之间的功能异质性可以通过基于FoxP 3和CD 45 RA的表达将Treg分成不同的亚群来阐明。本研究旨在探讨Treg亚群在初治SSc免疫失衡中的作用。采用流式细胞术分析31例SSc患者和33例健康对照者外周血单个核细胞（PBMC）的CD 4、CD 25、CD 45 RA、CTLA-4、FoxP 3和IL-17表达。在共培养实验中测量Treg免疫抑制能力。通过实时PCR测量FoxP 3、CTLA-4、IL-17 A和RORC mRNA的表达。在免疫抑制能力降低的SSc患者中，CD 4 + CD 25 + FoxP 3 + Treg细胞的频率显著升高（3.62±1.14 vs 1.97±0.75，p<0.001）。在SSc中，FoxP 3 highCD 45 RA −活化Treg细胞（aTreg）的比例降低，FoxP 3 lowCD 45 RA − T细胞的比例增加，FoxP 3 lowCD 45 RA+静息Treg细胞（rTreg）的比例降低。aTreg和rTreg的免疫抑制能力减弱，而FoxP 3lowCD 45 RA-T细胞表现出缺乏抑制能力。aTreg的免疫功能紊乱伴随着CTLA-4的异常表达。Th 17细胞数量在SSc中升高，FoxP 3lowCD 45 RA-T细胞产生IL-17，证实其Th 17潜能，这与SSc中FoxP 3 +IL-17+细胞水平升高一致。aTreg水平的降低，沿着功能缺陷，以及FoxP 3 lowCD 45 RA − T细胞比例的增加，是SSc患者中功能失调Treg增加的原因，可能导致Treg和Th 17细胞之间的免疫失衡。
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. 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. 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 FoxP3highCD45RA− activated Treg cells (aTreg) was decreased, the proportion of FoxP3lowCD45RA− T cells was increased, and the proportion of FoxP3lowCD45RA+ resting Treg cells (rTreg) was decreased. The immune suppression capacity of aTreg and rTreg was diminished, while FoxP3lowCD45RA− 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, FoxP3lowCD45RA− T cells produced IL-17, confirming their Th17 potential, which was consistent with the elevated levels of FoxP3+IL-17+ cells in SSc. A decrease in aTreg levels, along with functional deficiency, and an increase in the proportion of FoxP3lowCD45RA− T cells, was the reason for the increase in dysfunctional Treg in SSc patients, potentially causing the immune imbalance between Treg and Th17 cells.
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DOI：
10.1126/science.1202947
发表时间：
2011-04-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Qureshi OS;Zheng Y;Nakamura K;Attridge K;Manzotti C;Schmidt EM;Baker J;Jeffery LE;Kaur S;Briggs Z;Hou TZ;Futter CE;Anderson G;Walker LS;Sansom DM
通讯作者：
Sansom DM
影响因子：
4.4
作者：
Li, Ruobing;Perez, Nicolas;Vasu, Chenthamarakshan
通讯作者：
Vasu, Chenthamarakshan
DOI：
10.1016/j.prostaglandins.2006.12.003
发表时间：
2007-06-01
影响因子：
2.9
作者：
Kurusu, Shiro;Sakaguchi, Shinya;Kawaminami, Mitsumori
通讯作者：
Kawaminami, Mitsumori
影响因子：
4
作者：
Rajaee, A.;Ebrahimi, A.;Ghaderi, A.
通讯作者：
Ghaderi, A.
影响因子：
5.5
作者：
Abraham, D. J.;Krieg, T.;Distler, O.
通讯作者：
Distler, O.