Direct regulation of Gata3 expression determines the T helper differentiation potential of notch
Direct regulation of Gata3 expression determines the T helper differentiation potential of notch
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DOI：
10.1016/j.immuni.2007.05.021
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发表时间：
2007-07-01
期刊：
影响因子：
32.4
通讯作者：
Flavell, Richard A.
中科院分区：
文献类型：
--
作者：
Amsen, Derk;Antov, Andrey;Flavell, Richard A.
CD4(+) T辅助细胞分化为T辅助1 （Th1）或Th2效应细胞系，它们协调对不同类型微生物的免疫。Notch可以诱导Th1和Th2分化，但是什么决定了这些程序中的哪一个被激活以响应Notch尚不清楚。通过T细胞特异性基因消融Notch效应因子RBP-J或Notch1和2受体，我们发现CD4+ T细胞对寄生虫抗原的生理Th2反应需要Notch。GATA-3对于Notch诱导的Th2分化是必需的，我们确定了一个上游Gata3启动子作为Notch信号的直接靶点。此外，GATA-3的缺失使Notch从Th2诱导剂转变为Th1分化的强大诱导剂。因此，GaW是决定诱导Th2分化和限制Th1通过Notch分化的关键因素。
CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4+ T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, GaW is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch.