Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity.

Abstract

Regulatory T (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, here we show that IL-27 is specifically produced by intestinal Treg cells to regulate Th17 immunity. Selectively increased intestinal Th17 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+TCF1+ Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a novel 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.

• Authors: Chia-Hao Lin, Cheng-Jang Wu, Sunglim Cho, Rasika Patkar, Ling-Li Lin, Mei-Chi Chen, Elisabeth Israelsson, Joanne Betts, Magdalena Niedzielska, Shefali A Patel, Han G Duong, Romana R Gerner, Chia-Yun Hsu, Matthew Catley, Rose A Maciewicz, Hiutung Chu, Manuela Raffatellu, John T Chang, Li-Fan Lu
• Journal: bioRxiv : the preprint server for biology (bioRxiv) (Feb 21 2023) United States
• PMID: 36865314 (Publication Type: Preprint)