调节性 T 细胞（Treg 细胞）有助于建立免疫耐受。然而，Treg 细胞在给定组织中控制特定类型免疫反应的精确效应机制仍未解决。通过同时研究系统自身免疫下不同组织来源的Treg细胞，在本研究中，我们表明白细胞介素（IL）-27是由肠道Treg细胞特异性产生的，可调节辅助T17细胞（TH17细胞）免疫。通过 Treg 细胞特异性 IL-27 消融，选择性增加小鼠肠道 TH17 细胞反应，导致肠道炎症和结肠炎相关癌症加剧，但也有助于预防肠道细菌感染。此外，单细胞转录组分析已鉴定出 CD83 CD62Llo Treg 细胞亚群，该亚群与之前鉴定为主要 IL-27 产生者的肠道 Treg 细胞群不同。总的来说，我们的研究揭示了一种新的 Treg 细胞抑制机制，对于控制特定组织中特定类型的免疫反应至关重要，并为组织特异性 Treg 细胞介导的免疫调节提供了进一步的机制见解。© 2023。作者，下施普林格自然美国公司的独家许可

Regulatory T cells (Treg cells) are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Treg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Treg cells from different tissue origins under systemic autoimmunity, in the present study we show that interleukin (IL)-27 is specifically produced by intestinal Treg cells to regulate helper T17 cell (TH17 cell) immunity. Selectively increased intestinal TH17 cell responses in mice with Treg cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83+CD62Llo Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a new Treg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue and provides further mechanistic insights into tissue-specific Treg cell-mediated immune regulation.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.