Critical regulation of early Th17 cell differentiation by interleukin-1 signaling.
Critical regulation of early Th17 cell differentiation by interleukin-1 signaling.
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DOI：
10.1016/j.immuni.2009.02.007
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发表时间：
2009-04-17
期刊：
影响因子：
32.4
通讯作者：
Dong, Chen
中科院分区：
文献类型：
--
作者：
Chung, Yeonseok;Chang, Seon Hee;Martinez, Gustavo J.;Yang, Xuexian O.;Nurieva, Roza;Kang, Hong Soon;Ma, Li;Watowich, Stephanie S.;Jetten, Anton M.;Tian, Qiang;Dong, Chen
Th 17细胞最近在小鼠和人类中都被发现。尽管IL-1在人Th 17细胞分化中具有重要作用，但其潜在机制知之甚少，但其在小鼠中的功能尚不清楚。在这里，我们表明，IL-1 R1在T细胞中的表达，这是由IL-6诱导，是必要的Th 17介导的自身免疫和早期Th 17在体内分化。此外，树突状细胞介导的Th 17从幼稚或调节前体分化需要T细胞中的IL-1信号传导，并且IL-1与IL-6和IL-23协同调节Th 17分化并维持效应Th 17细胞中的细胞因子表达。重要的是，IL-1在Th 17分化过程中调节IRF 4和RORγt的表达;这两个因子的过度表达导致IL-1非依赖性Th 17极化。因此，我们的数据表明IL-1在Th 17分化中的关键作用，并且该途径可以作为Th 17介导的免疫病理学的新靶点。
Th17 cells have been recently discovered in both mouse and human. Although IL-1 has been shown to be important in human Th17 cell differentiation with little knowledge of the underlying mechanism, its function in mouse is less clear. Here we show that IL-1R1 expression in T cells, which was induced by IL-6, was necessary for Th17-mediated autoimmunity and for early Th17 differentiation in vivo. Moreover, IL-1 signaling in T cells was required in dendritic cell-mediated Th17 differentiation from naïve or regulatory precursors and IL-1 synergized with IL-6 and IL-23 to regulate Th17 differentiation and maintain cytokine expression in effector Th17 cells. Importantly, IL-1 regulated the expression of IRF4 and RORγt during Th17 differentiation; over-expression of these two factors resulted in IL-1-independent Th17 polarization. Our data thus indicate a critical role of IL-1 in Th17 differentiation and this pathway may serve as a novel target for Th17-mediated immunopathology.
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