Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells
Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells
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DOI：
10.1073/pnas.0600666103
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发表时间：
2006-05-23
影响因子：
11.1
通讯作者：
O'Shea, John J.
中科院分区：
文献类型：
--
作者：
Chen, Zhi;Laurence, Arian;O'Shea, John J.
细胞因子信号传导（SOCS）3的抑制剂是一种具有关键但选择性细胞特异性作用的细胞因子诱导剂。我们表明，T细胞中SOCS3的缺乏对T细胞与T辅助器（Th）1或Th2子集的分化具有最小的影响。因此，SOCS3对IL-12依赖性信号换能器和转录激活因子（STAT）4磷酸化或IL-4依赖性STAT6磷酸化没有影响。相比之下，发现SOCS3是IL-23介导的STAT3磷酸化和Th17生成的主要调节剂，而STAT3直接与IL-17A和IL-17F启动子结合。我们得出的结论是，SOCS3是IL-23信号传导的基本负调节剂，抑制其限制了Th17分化的产生。
Suppressor of cytokine signaling (Socs) 3 is a cytokine-inducible inhibitor with critical but selective cell-specific effects. We show that deficiency of Socs3 in T cells had minimal effects on differentiation of T cells to the T helper (Th) 1 or Th2 subsets; accordingly, Socs3 had no effect on IL-12-dependent signal transducer and activator of transcription (Stat) 4 phosphorylation or IL-4-dependent Stat6 phosphorylation. By contrast, Socs3 was found to be a major regulator of IL-23-mediated Stat3 phosphorylation and Th17 generation, and Stat3 directly binds to the IL-17A and IL-17F promoters. We conclude that Socs3 is an essential negative regulator of IL-23 signaling, inhibition of which constrains the generation of Th17 differentiation.