美国加州大学洛杉矶分校Li-Fan Lu团队发现，肠道调节性T细胞的选择性分泌IL-27允许对T_H17细胞免疫进行肠道特异性调节。相关论文于2023年11月6日在线发表于国际学术期刊《自然—免疫学》。

研究人员通过同时研究全身自身免疫情况下不同组织来源的调节性T细胞（T_reg细胞），发现肠道T_reg细胞特异性地产生白细胞介素（IL）-27来调节辅助性T17细胞（T_H17 细胞）免疫。T_reg细胞特异性IL-27敲减后，小鼠肠道T_H17细胞反应选择性增加，导致肠道炎症和结肠炎相关癌症恶化，但也有助于保护肠道免受细菌感染。此外，单细胞转录组分析还发现了一个CD83⁺CD62L^lo T_reg细胞亚群，该亚群是IL-27的主要产生者，有别于以前的肠T_reg细胞群。

总之，这项研究发现了一种新的T_reg细胞抑制机制，它对控制特定组织中的特定类型免疫反应至关重要，并为组织特异性T_reg细胞介导的免疫调节提供了进一步的机理见解。

据悉，T_reg细胞有助于建立免疫耐受。然而，T_reg细胞在特定组织中控制特定类型免疫反应的精确效应机制仍未得到解决。

附：英文原文

Title: Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of TH17 cell immunity

Author: Lin, Chia-Hao, Wu, Cheng-Jang, Cho, Sunglim, Patkar, Rasika, Huth, William J., Lin, Ling-Li, Chen, Mei-Chi, Israelsson, Elisabeth, Betts, Joanne, Niedzielska, Magdalena, Patel, Shefali A., Duong, Han G., Gerner, Romana R., Hsu, Chia-Yun, Catley, Matthew, Maciewicz, Rose A., Chu, Hiutung, Raffatellu, Manuela, Chang, John T., Lu, Li-Fan

Issue&Volume: 2023-11-06

Abstract: 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. Regulatory T (Treg) cells are functionally heterogeneous, yet how each Treg cell subset exerts its suppressor function remains unresolved. Lin et al. identify IL-27 as a key Treg cell effector molecule selectively required for gut TH17 cell regulation.

DOI: 10.1038/s41590-023-01667-y

Source: https://www.nature.com/articles/s41590-023-01667-y