TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine
TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine
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DOI：
10.1038/mi.2017.5
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发表时间：
2017-11-01
影响因子：
8
通讯作者：
Esplugues, E.
中科院分区：
文献类型：
--
作者：
Pascual-Reguant, A.;Sarmadi, J. Bayat;Esplugues, E.
T（H）17细胞是炎症的主要驱动因素，并参与多种自身免疫性疾病。组织炎症是一种有益的宿主对感染的反应，但它也可能导致自身免疫。炎症反应期间组织和免疫系统之间的串扰是保持组织完整性和恢复生理过程的关键。然而，炎症组织如何通过控制促炎性T细胞来调节免疫反应的大小，到目前为止还没有得到很好的表征。在这里，我们表明，T（H）17细胞积累在小肠炎症表达IL-33受体（ST 2）和肠上皮细胞（IEC）的主要来源的警报白细胞介素-33（IL-33）。我们表明，促炎性T（H）17细胞获得的调节表型与免疫抑制特性响应IL-33。ST 2信号传导的缺乏促进T（H）17细胞分泌促炎细胞因子并抑制IL-10的分泌。我们的研究结果为IEC通过IL-33/ST 2轴控制小肠中的促炎性T（H）17细胞以维持稳态的机制提供了新的见解。
T(H)17 cells are major drivers of inflammation and involved in several autoimmune diseases. Tissue inflammation is a beneficial host response to infection, but it can also contribute to autoimmunity. The crosstalk between a tissue and the immune system during an inflammatory response is key for preserving tissue integrity and restoring physiological processes. However, how the inflamed tissue regulates the magnitude of an immune response by controlling pro-inflammatory T cells is not well characterized so far. Here we show that T(H)17 cells accumulating in the small intestine upon inflammation express the IL-33 receptor (ST2) and intestinal epithelial cells (IEC) are the main source of the alarmin interleukin-33 (IL-33). We show that pro-inflammatory T(H)17 cells acquire a regulatory phenotype with immunosuppressive properties in response to IL-33. Absence of ST2 signaling promotes the secretion of pro-inflammatory cytokines by T(H)17 cells and dampens the secretion of IL-10. Our results provide new insights into the mechanisms by which IEC, via IL-33/ST2 axis, may control pro-inflammatory T(H)17 cells in the small intestine to sustain homeostasis.