Chen Zhi, Laurence Arian, Kanno Yuka, Pacher-Zavisin Margit, Zhu Bing-Mei, Tato Cristina, Yoshimura Akihiko, Hennighausen Lothar, O'Shea John J
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2006 May 23;103(21):8137-42. doi: 10.1073/pnas.0600666103. Epub 2006 May 12.
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.
细胞因子信号转导抑制因子（Socs）3是一种细胞因子诱导型抑制剂，具有关键但具有选择性的细胞特异性作用。我们发现，T细胞中Socs3的缺乏对T细胞向辅助性T细胞（Th）1或Th2亚群的分化影响极小；因此，Socs3对依赖白细胞介素-12（IL-12）的信号转导及转录激活因子（Stat）4磷酸化或依赖IL-4的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生成的主要调节因子，并且Stat3直接与IL-17A和IL-17F启动子结合。我们得出结论，Socs3是IL-23信号传导的重要负调节因子，抑制它会限制Th17分化的产生。
