Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms
Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms
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DOI：
10.15252/embr.201338233
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发表时间：
2014-09-01
期刊：
影响因子：
7.7
通讯作者：
Macian, Fernando
中科院分区：
文献类型：
--
作者：
Shin, Daniel S.;Jordan, Ayana;Macian, Fernando
调节性T细胞（TCRs）通过抑制活化诱导的增殖和细胞因子表达来控制自身反应性T细胞。负责由Tcl4失活效应T细胞的分子机制仍有待充分表征。我们报告说，T辅助细胞的刺激，在THEOTH的存在下迅速激活NFAT 1，并增加NFAT 1依赖的转录抑制子Ikaros的表达。NFAT 1缺陷或显性阴性Ikaros损害Treg介导的体外和体内T辅助细胞抑制。因此，我们的研究结果将NFAT依赖性机制作为T细胞耐受性的一般调节因子，并表明Treg介导的T辅助细胞抑制是由NFAT调节的基因表达激活引起的。
Regulatory T cells (Tregs) control autoreactive T cells by inhibiting activation-induced proliferation and cytokine expression. The molecular mechanisms responsible for the inactivation of effector T cells by Tregs remain yet to be fully characterized. We report that T-helper cells stimulated in the presence of Tregs quickly activate NFAT1 and have increased NFAT1-dependent expression of the transcription repressor Ikaros. NFAT1 deficiency or dominant-negative Ikaros compromises Treg-mediated inhibition of T-helper cells in vitro and in vivo. Thus, our results place NFAT-dependent mechanisms as general regulators of T-cell tolerance and show that Treg-mediated suppression of T-helper cells results from the activation of NFAT-regulated gene expression.