Deficient SOCS3 expression in CD4+CD25+FoxP3+ regulatory T cells and SOCS3-mediated suppression of Treg function
Deficient SOCS3 expression in CD4+CD25+FoxP3+ regulatory T cells and SOCS3-mediated suppression of Treg function
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DOI：
10.1002/eji.200737193
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发表时间：
2007-08-01
影响因子：
5.4
通讯作者：
Ray, Anuradha
中科院分区：
文献类型：
--
作者：
Pillemer, Brendan B. L.;Xu, Hui;Ray, Anuradha
天然存在的CD 4（+）CD 25（+）FoxP 3（+）调节性T细胞（Treg）抑制T辅助（Th）细胞介导的免疫应答。已知细胞因子IL-2和IL-6影响Treg功能。然而，它们对Th细胞相对于Treg的相对作用还不清楚。用IL-2刺激，以及在较小程度上用IL-6刺激，增强了Treg增殖、FoxP 3和CTLA 4维持以及抑制功能。相反，当IL-2或IL-6加入Treg/Th细胞共培养物时，抑制被抑制。分子SOCS 3负调节对IL-2和IL-6的应答。有趣的是，与Th细胞不同，发现Treg缺乏SOCS 3蛋白表达。这一发现的意义在于Treg需要快速响应这些细胞因子，以防止对自身抗原的不必要的免疫应答。SOCS 3在Treg中的过表达降低了它们的增殖、FoxP 3和CTLA-4的表达以及抑制功能。因此，在需要抑制Treg的疾病中，SOCS 3表达的上调可能是有用的治疗方法。
Naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg) suppress T helper (Th) cell-mediated immune responses. The cytokines IL-2 and IL-6 are known to influence Treg function. However, their relative effects on Th cells versus Treg are not well understood. Stimulation with IL-2, and to a lesser extent, IL-6, enhanced Treg proliferation, FoxP3 and CTLA4 maintenance, and suppressive function. In contrast, when IL-2 or IL-6 were added to Treg/Th cell cocultures, suppression was inhibited. The molecule SOCS3 negatively regulates responses to IL-2 and IL-6. Interestingly, unlike Th cells, Treg were found to be deficient in SOCS3 protein expression. The significance of this finding lies in the need for Treg to rapidly respond to these cytokines to prevent unwarranted immune responses to self-antigens. Overexpression of SOCS3 in Treg decreased their proliferation, FoxP3 and CTLA-4 expression and suppressive function. Thus, up-regulation of SOCS3 expression may be a useful therapeutic approach in diseases where inhibition of Treg is desirable.