PMID: 15240659Jul 9, 2004Paper

Cell proliferation and STAT6 pathways are negatively regulated in T cells by STAT1 and suppressors of cytokine signaling

The Journal of Immunology : Official Journal of the American Association of Immunologists
Cheng-Rong YuCharles E Egwuagu

Abstract

Suppressor of cytokine signaling (SOCS) proteins have emerged as important regulators of cytokine signals in lymphocytes. In this study, we have investigated regulation of SOCS expression and their role in Th cell growth and differentiation. We show that SOCS genes are constitutively expressed in naive Th cells, albeit at low levels, and are differentially induced by Ag and Th-polarizing cytokines. Whereas cytokines up-regulate expression of SOCS1, SOCS2, SOCS3, and cytokine-induced Src homology 2 protein, Ags induce down-regulation of SOCS3 within 48 h of Th cell activation and concomitantly up-regulate SOCS1, SOCS2, and cytokine-induced Src homology 2 protein expression. We further show that STAT1 signals play major roles in inducing SOCS expression in Th cells and that induction of SOCS expression by IL-4, IL-12, or IFN-gamma is compromised in STAT1-deficient primary Th cells. Surprisingly, IL-4 is a potent inducer of STAT1 activation in Th2 but not Th1 cells, and SOCS1 or SOCS3 expression is dramatically reduced in STAT1(-/-) Th2 cells. To our knowledge, this is the first report of IL-4-induced STAT1 activation in Th cells, and suggests that its induction of SOCS, may in part, regulate IL-4 functions in Th2 cells. In fact, ...Continue Reading

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Citations

Apr 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zamaneh MikhakAndrew D Luster
Apr 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xuebin LiuCharles E Egwuagu
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Jul 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cheng-Rong YuCharles E Egwuagu
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