mTOR Mediates IL-23 Induction of Neutrophil IL-17 and IL-22 Production.
mTOR Mediates IL-23 Induction of Neutrophil IL-17 and IL-22 Production.
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DOI：
10.4049/jimmunol.1501541
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发表时间：
2016-05-15
期刊：
影响因子：
--
通讯作者：
Cong Y
中科院分区：
文献类型：
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作者：
Chen F;Cao A;Yao S;Evans-Marin HL;Liu H;Wu W;Carlsen ED;Dann SM;Soong L;Sun J;Zhao Q;Cong Y
最近的研究表明，中性粒细胞能够产生 IL-22 和 IL-17，对炎症性肠病 (IBD) 的发病机制进行差异调节。然而，目前尚不清楚中性粒细胞产生IL-22和IL-17是如何调节的，以及它们在IBD发病机制中的作用。在这项研究中，我们发现IL-23促进中性粒细胞产生IL-17和IL-22。 IL-23刺激中性粒细胞表达IL-23受体以及rorc和ahr。 RORγt 和 AhR 差异调节 IL-23 对中性粒细胞 IL-17 和 IL-22 的诱导。此外，IL-23 诱导中性粒细胞中 mTOR 的激活。阻断 mTOR 通路可抑制 IL-23 诱导的 rorc 和 ahr 表达以及 IL-17 和 IL-22 产生。通过利用微生物抗原特异性 T 细胞介导的结肠炎模型，我们证明中性粒细胞的消耗以及 IL-22 的阻断会导致结肠炎严重程度的显着增加，从而表明中性粒细胞和 IL-22 在慢性结肠炎中的保护作用。总的来说，我们的数据显示，中性粒细胞负向调节结肠炎的微生物抗原特异性 T 细胞诱导，IL-23 通过诱导 rorc 和 ahr 诱导中性粒细胞产生 IL-22 和 IL-17，这是由 mTOR 途径介导的。
It has been shown recently that neutrophils are able to produce IL-22 and IL-17, which differentially regulate the pathogenesis of inflammatory bowel disease (IBD). However, it is still largely unknown how the neutrophil production of IL-22 and IL-17 is regulated, and their role in the pathogenesis of IBD. In this study, we found that IL-23 promoted neutrophil production of IL-17 and IL-22. IL-23 stimulated the neutrophil expression of IL-23 receptor as well as rorc and ahr. RORγt and AhR differentially regulated IL-23 induction of neutrophil IL-17 and IL-22. Additionally, IL-23 induced the activation of mTOR in neutrophils. Blockade of mTOR pathway inhibited IL-23-induced expression of rorc and ahr as well as IL-17 and IL-22 production. By utilizing a microbiota antigen specific T-cell mediated colitis model, we demonstrated that depletion of neutrophils, as well as blockade of IL-22, resulted in a significant increase in the severity of colitis, thereby indicating a protective role of neutrophils and IL-22 in chronic colitis. Collectively, our data revealed that neutrophils negatively regulate microbiota antigen specific T cell induction of colitis, and IL-23 induces neutrophil production of IL-22 and IL-17 through induction of rorc and ahr, which is mediated by mTOR pathway.