Intestinal microbiota-specific Th17 cells possess regulatory properties and suppress effector T cells via c-MAF and IL-10.
Intestinal microbiota-specific Th17 cells possess regulatory properties and suppress effector T cells via c-MAF and IL-10.
复制标题
肠道微生物群特异性 Th17 细胞具有调节特性，并通过 c-MAF 和 IL-10 抑制效应 T 细胞。
DOI：
10.1016/j.immuni.2023.11.003
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发表时间：
2023
期刊：
影响因子：
32.4
通讯作者：
Ivanov,IvayloI
中科院分区：
文献类型：
--
作者：
Brockmann,Leonie;Tran,Alexander;Huang,Yiming;Edwards,Madeline;Ronda,Carlotta;Wang,HarrisH;Ivanov,IvayloI
共生微生物诱导产生精氨酸的效应组织驻留的CD 4 +T细胞，但这些T细胞在粘膜稳态中的功能尚不清楚。在这里，我们报告说，肠道特异性Th 17细胞具有抗炎表型的白细胞介素（IL）-10和共抑制受体的表达为标志。肠道驻留的直肠特异性Th 17细胞的抗炎表型由转录因子c-MAF驱动。产生IL-10的肠道特异性Th 17细胞是异质性的，来源于TCF 1+肠道驻留祖细胞Th 17细胞群。Th 17细胞在小肠固有层中获得IL-10表达和抗炎表型。CD 4 +T细胞的IL-10产生和肠巨噬细胞中的IL-10信号传导驱动了肠道特异性Th 17细胞的IL-10表达。小肠黏膜特异性Th 17细胞具有免疫调节功能，在体外和体内以IL-10依赖和c-MAF依赖的方式抑制效应T细胞的活性。我们的研究结果表明，组织驻留粘膜特异性Th 17细胞执行粘膜稳态的调节功能。
Commensal microbes induce cytokine-producing effector tissue-resident CD4+T cells, but the function of these T cells in mucosal homeostasis is not well understood. Here, we report that commensal-specific intestinal Th17 cells possess an anti-inflammatory phenotype marked by expression of interleukin (IL)-10 and co-inhibitory receptors. The anti-inflammatory phenotype of gut-resident commensal-specific Th17 cells was driven by the transcription factor c-MAF. IL-10-producing commensal-specific Th17 cells were heterogeneous and derived from a TCF1+gut-resident progenitor Th17 cell population. Th17 cells acquired IL-10 expression and anti-inflammatory phenotype in the small-intestinal lamina propria. IL-10 production by CD4+T cells and IL-10 signaling in intestinal macrophages drove IL-10 expression by commensal-specific Th17 cells. Intestinal commensal-specific Th17 cells possessed immunoregulatory functions and curbed effector T cell activityin vitroandin vivoin an IL-10-dependent and c-MAF-dependent manner. Our results suggest that tissue-resident commensal-specific Th17 cells perform regulatory functions in mucosal homeostasis.