Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells
Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells
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DOI：
10.1073/pnas.0804231105
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发表时间：
2008-07-15
影响因子：
11.1
通讯作者：
Kishimoto, Tadamitsu
中科院分区：
文献类型：
--
作者：
Kimura, Akihiro;Naka, Tetsuji;Kishimoto, Tadamitsu
产生IL-17的辅助性T细胞（Th 17）最近被鉴定为以前未描述的辅助性T细胞亚群。在这里，我们证明，芳烃受体（Ahr）在Th 17细胞的承诺具有重要的调节功能。Ahr在Th 17极化条件下被强烈诱导。Ahr缺陷的初始T细胞在由TGF-β加IL-6诱导时表现出分化成Th 17细胞的能力的相当大的损失。我们能够证明Ahr与Stat 1和Stat 5相互作用，这两个因子负调节Th 17的发育。而在用TGF-β加IL-6刺激后24小时，Ahr野生型幼稚T细胞中的Stat 1活化恢复到其基础水平，而刺激后，Stat 1在Ahr缺陷型幼稚T细胞中保持活化。这些结果表明，Ahr通过调节Stat 1活化参与Th 17细胞分化，这一发现构成了调节Th 17细胞发育的额外机制。
IL-17-producing T helper cells (Th17) have been recently identified as a previously undescribed subset of helper T cells. Here, we demonstrate that aryl hydrocarbon receptor (Ahr) has an important regulatory function in the commitment of Th17 cells. Ahr was robustly induced under Th17-polarizing conditions. Ahr-deficient naive T cells showed a considerable loss in the ability to differentiate into Th17 cells when induced by TGF-beta plus IL-6. We were able to demonstrate that Ahr interacts with Stat1 and Stat5, which negatively regulate Th17 development. Whereas Stat1 activation returned to its basal level in Ahr wild type naive T cells 24 h after stimulation with TGF-beta plus IL-6, Stat1 remained activated in Ahr-deficient naive T cells after stimulation. These results indicate that Ahr participates in Th17 cell differentiation through regulating Stat1 activation, a finding that constitutes additional mechanisms in the modulation of Th17 cell development.