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 activity in vitro and in vivo in 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.

共生微生物诱导产生细胞因子的效应组织驻留的 CD4⁺ 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，我们报道了共生特异性肠 Th17 细胞具有以白细胞介素 （IL）-10 和共抑制受体表达为特征的抗炎表型。肠道驻留共体特异性 Th17 细胞的抗炎表型由转录因子 c-MAF 驱动。产生 IL-10 的共生特异性 Th17 细胞是异质性的，来源于 TCF1 ⁺ 肠道驻留祖细胞 Th17 细胞群。Th17 细胞在小肠固有层中获得 IL-10 表达和抗炎表型。CD4+ T 细胞产生的 IL-10 和肠道巨噬细胞中的 IL-10 信号传导驱动共生特异性 Th17 细胞的 IL-10 表达。肠道共生特异性 Th17 细胞在体外 和体内以 IL-10 依赖性和 c-MAF 依赖性方式抑制效应 T 细胞活性 。我们的结果表明，组织驻留的共生特异性 Th17 细胞在粘膜稳态中发挥调节功能。