The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-β and suppresses T(H)2 differentiation.
The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-β and suppresses T(H)2 differentiation.
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DOI：
10.1038/ni.2362
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发表时间：
2012-07-01
影响因子：
30.5
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
--
作者：
Kuwahara, Makoto;Yamashita, Masakatsu;Shinoda, Kenta;Tofukuji, Soichi;Onodera, Atsushi;Shinnakasu, Ryo;Motohashi, Shinichiro;Hosokawa, Hiroyuki;Tumes, Damon;Iwamura, Chiaki;Lefebvre, Veronique;Nakayama, Toshinori
SOX4是一种转录因子，调节多种发育过程。在这里，我们发现SOX4是由转化生长因子β诱导的，并通过两种不同的机制负调控转录因子GATA-3，转录因子GATA-3是辅助性T细胞功能的主要调节因子。首先，Sox4直接与GATA-3结合，阻止其与GATA-3共识DNA序列结合。其次，Sox4结合到编码IL-5(一种TH2细胞因子)基因的启动子区域，并阻止GATA-3与该启动子的结合。Th2细胞驱动的气道炎症受Sox4表达变化的调节。因此，Sox4可作为转化生长因子β的下游靶点，抑制GATA-3功能、TH2分化和TH2细胞介导的炎症反应。
Sox4 is a transcription factor that regulates various developmental processes. Here we show that Sox4 was induced by TGF-β and negatively regulated the transcription factor GATA-3, the master regulator of function of T helper type 2 (TH2) cells, by two distinct mechanisms. First, Sox4 bound directly to GATA-3, preventing its binding to GATA-3 consensus DNA sequences. Second, Sox4 bound to the promoter region of the gene encoding interleukin 5 (IL-5), a TH2 cytokine, and prevented binding of GATA-3 to this promoter. TH2 cell–driven airway inflammation was modulated by alterations in Sox4 expression. Thus, Sox4 acted as a downstream target of TGF-β to inhibit GATA-3 function, TH2 differentiation and TH2 cell–mediated inflammation.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
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作者：
Inami, M;Yamashita, M;Nakayama, T
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Nakayama, T
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Gorelik, L;Flavell, RA
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Flavell, RA
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Hossain, Mohammad B.;Hosokawa, Hiroyuki;Nakayama, Toshinori
通讯作者：
Nakayama, Toshinori
影响因子：
32.4
作者：
Miaw, SC;Choi, A;Ho, IC
通讯作者：
Ho, IC