Regulation of interferon gamma signaling by suppressors of cytokine signaling and regulatory T cells.
Regulation of interferon gamma signaling by suppressors of cytokine signaling and regulatory T cells.
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DOI：
10.3389/fimmu.2013.00469
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发表时间：
2013-12-18
影响因子：
7.3
通讯作者：
Johnson HM
中科院分区：
文献类型：
--
作者：
Larkin J 3rd;Ahmed CM;Wilson TD;Johnson HM
调节性 T 细胞 (Treg) 在预防自身免疫性疾病中发挥着不可或缺的作用，因为在缺乏调节性 T 细胞 (Treg) 的情况下，干扰素 γ (IFNγ) 介导的致命性自身免疫就会发生（在小鼠和人类中）。此外，Treg 还参与预防与异常 IFNγ 信号传导相关的自身免疫和自身炎症性疾病的发生，例如 1 型糖尿病、狼疮和脂多糖 (LPS) 介导的内毒素血症。值得注意的是，细胞因子信号传导抑制因子 1 缺陷 (SOCS1−/−) 小鼠也会死于致命的自身炎症性疾病，主要是过度的 IFNγ 信号传导，并且具有与 Treg 缺陷小鼠相似的病程动力学。此外，SOCS1 缺陷与狼疮进展有关，并增加对 LPS 介导的内毒素血症的易感性。尽管已经确定Treg和SOCS1在IFNγ信号传导的调节和致命性自身炎症性疾病的预防中发挥着关键作用，但Treg/SOCS1串扰在IFNγ信号传导调节中的作用基本上尚未被探索。这是特别相关的，因为最近的出版物暗示了 SOCS1 在外周 Tregs 稳定性中的作用。本综述将探讨新兴的研究结果，这些发现表明 SOCS1 和 Treg 调控途径的交叉在控制 IFN γ 信号传导和免疫系统功能中发挥着关键作用。
Regulatory T cells (Tregs) play an indispensable role in the prevention of autoimmune disease, as interferon gamma (IFNγ) mediated, lethal auto-immunity occurs (in both mice and humans) in their absence. In addition, Tregs have been implicated in preventing the onset of autoimmune and auto-inflammatory conditions associated with aberrant IFNγ signaling such as type 1 diabetes, lupus, and lipopolysaccharide (LPS) mediated endotoxemia. Notably, suppressor of cytokine signaling-1 deficient (SOCS1−/−) mice also succumb to a lethal auto-inflammatory disease, dominated by excessive IFNγ signaling and bearing similar disease course kinetics to Treg deficient mice. Moreover SOCS1 deficiency has been implicated in lupus progression, and increased susceptibility to LPS mediated endotoxemia. Although it has been established that Tregs and SOCS1 play a critical role in the regulation of IFNγ signaling, and the prevention of lethal auto-inflammatory disease, the role of Treg/SOCS1 cross-talk in the regulation of IFNγ signaling has been essentially unexplored. This is especially pertinent as recent publications have implicated a role of SOCS1 in the stability of peripheral Tregs. This review will examine the emerging research findings implicating a critical role of the intersection of the SOCS1 and Treg regulatory pathways in the control of IFN gamma signaling and immune system function.