Dendritic cell MST1 inhibits Th17 differentiation.
Dendritic cell MST1 inhibits Th17 differentiation.
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DOI：
10.1038/ncomms14275
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发表时间：
2017-02-01
影响因子：
16.6
通讯作者：
Liu G
中科院分区：
文献类型：
--
作者：
Li C;Bi Y;Li Y;Yang H;Yu Q;Wang J;Wang Y;Su H;Jia A;Hu Y;Han L;Zhang J;Li S;Tao W;Liu G
尽管对CD4+T细胞的分化进行了广泛的研究，但对抗原提呈细胞依赖的T细胞的调节机制尚不清楚。在这里，我们研究了依赖于树突状细胞(DC)的T细胞分化在自身免疫和抗真菌炎症中的作用，并发现来自DC的哺乳动物不育20-样蛋白1(MST1)信号负向调节IL-17产生的CD4+T辅助细胞(Th17)分化。树突状细胞MST1缺乏可增加CD4+T细胞产生IL-17，而树突状细胞异位表达MST1则抑制其产生IL-17。值得注意的是，MST1介导的DC依赖的Th17分化调节实验性自身免疫性脑脊髓炎和抗真菌免疫。在机制上，MST1缺陷的DC在诱导Th17分化的过程中，促进IL-6的分泌，调节IL-6受体α/β和STAT3的激活。P38MAPK信号的激活是MST1缺陷DC产生IL-6的原因。因此，我们的结果确定了DC MST1-p38MAPK信号通路在引导Th17分化中的作用。Th17细胞的分化是感染和自身免疫的中心。在这里，作者表明，树突状细胞表达MST1限制了IL-6的产生，从而在对真菌感染和实验性自身免疫性脑脊髓炎的免疫中控制Th17的分化。
Although the differentiation of CD4+T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell (DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4+T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4+T cells, whereas ectopic MST1 expression in DCs inhibits it. Notably, MST1-mediated DC-dependent Th17 differentiation regulates experimental autoimmune encephalomyelitis and antifungal immunity. Mechanistically, MST1-deficient DCs promote IL-6 secretion and regulate the activation of IL-6 receptor α/β and STAT3 in CD4+T cells in the course of inducing Th17 differentiation. Activation of the p38 MAPK signal is responsible for IL-6 production in MST1-deficient DCs. Thus, our results define the DC MST1–p38MAPK signalling pathway in directing Th17 differentiation. The differentiation of Th17 cells is central to infection and autoimmunity. Here, the authors show that expression of MST1 by dendritic cells limits IL-6 production and thereby controls Th17 differentiation in immunity to fungal infection and experimental autoimmune encephalomyelitis.