Kimura Akihiro, Naka Tetsuji, Nohara Keiko, Fujii-Kuriyama Yoshiaki, Kishimoto Tadamitsu
Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, 1-3, Yamada-oka, Suita, Osaka 565-0871, Japan.
Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9721-6. doi: 10.1073/pnas.0804231105. Epub 2008 Jul 7.
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 naïve 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 naïve T cells 24 h after stimulation with TGF-beta plus IL-6, Stat1 remained activated in Ahr-deficient naïve 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.
产生白细胞介素-17的辅助性T细胞(Th17)最近被鉴定为一类先前未被描述的辅助性T细胞亚群。在此,我们证明芳烃受体(Ahr)在Th17细胞的分化过程中具有重要的调节功能。在Th17极化条件下,Ahr被强烈诱导。当由转化生长因子-β(TGF-β)加白细胞介素-6(IL-6)诱导时,缺乏Ahr的初始T细胞分化为Th17细胞的能力显著丧失。我们能够证明Ahr与信号转导和转录激活因子1(Stat1)以及信号转导和转录激活因子5(Stat5)相互作用,而Stat1和Stat5对Th17的发育起负调节作用。在用TGF-β加IL-6刺激24小时后,野生型Ahr初始T细胞中的Stat1激活恢复到基础水平,而在缺乏Ahr的初始T细胞受到刺激后,Stat1仍处于激活状态。这些结果表明,Ahr通过调节Stat1激活参与Th17细胞分化,这一发现构成了Th17细胞发育调控中的额外机制。