The Runx1 transcription factor inhibits the differentiation of naive CD4+ T cells into the Th2 lineage by repressing GATA3 expression

Runx1 转录因子通过抑制 GATA3 表达来抑制幼稚 CD4+ T 细胞向 Th2 谱系分化

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作者:Okiru Komine, Keitaro Hayashi, Waka Natsume, Toshio Watanabe, Youichi Seki, Noriyasu Seki, Ryoji Yagi, Wataru Sukzuki, Hidekazu Tamauchi, Katsuto Hozumi, Sonoko Habu, Masato Kubo, Masanobu Satake

Abstract

Differentiation of naive CD4+ T cells into helper T (Th) cells is controlled by a combination of several transcriptional factors. In this study, we examined the functional role of the Runx1 transcription factor in Th cell differentiation. Naive T cells from transgenic mice expressing a dominant interfering form of Runx1 exhibited enhanced interleukin 4 production and efficient Th2 differentiation. In contrast, transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression. Furthermore, endogenous expression of Runx1 in naive T cells declined after T cell receptor stimulation, at the same time that expression of GATA3 increased. We conclude that Runx1 plays a novel role as a negative regulator of GATA3 expression, thereby inhibiting the Th2 cell differentiation.

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