The transcription factor STAT3 is required for T helper 2 cell development.

The transcription factor STAT3 is required for T helper 2 cell development.
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DOI:
10.1016/j.immuni.2010.12.013
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发表时间:
2011-01-28
期刊:
影响因子:
32.4
通讯作者:
Kaplan MH
Kaplan MH
中科院分区:
医学1区
文献类型:
--
作者:
Stritesky GL;Muthukrishnan R;Sehra S;Goswami R;Pham D;Travers J;Nguyen ET;Levy DE;Kaplan MH

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信号转导和转录激活因子 (STAT) 家族成员指导 T 辅助细胞的分化,其中特定的 STAT 蛋白可促进不同的效应子亚群。 STAT6 是辅助 T 细胞 2 (Th2) 细胞发育所必需的,而 STAT3 则促进 Th17 和滤泡辅助 T 细胞亚群的分化。我们证明 STAT3 在 Th2 细胞发育过程中也被激活,并且是 Th2 细胞相关细胞因子和转录因子表达所必需的。 STAT3 直接与 Th2 细胞相关基因位点结合,并且是 STAT6 结合靶基因的能力所必需的。在体内,T细胞中STAT3的缺陷消除了用卵清蛋白或具有持续活性的STAT6的转基因致敏和攻击的小鼠的过敏性炎症。因此,STAT3与STAT6协同促进Th2细胞发育。这些结果表明,分化 T 辅助细胞在 Th2 细胞发育过程中整合了多个 STAT 蛋白信号。
Signal Transducer and Activator of Transcription (STAT) family members direct the differentiation of T helper cells, with specific STAT proteins promoting distinct effector subsets. STAT6 is required for the development of T helper 2 (Th2) cells, whereas STAT3 promotes differentiation of Th17 and follicular helper T cell subsets. We demonstrated that STAT3 was also activated during Th2 cell development and was required for the expression of Th2-cell associated cytokines and transcription factors. STAT3 bound directly to Th2-cell associated gene loci and was required for the ability of STAT6 to bind target genes. In vivo, STAT3-deficiency in T cells eliminated the allergic inflammation in mice sensitized and challenged with ovalbumin, or transgenic for constitutively active STAT6. Thus, STAT3 cooperates with STAT6 in promoting Th2 cell development. These results demonstrate that differentiating T helper cells integrate multiple STAT protein signals during Th2 cell development.
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