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

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.

• Authors: Chia-Hao Lin, Cheng-Jang Wu, Sunglim Cho, Rasika Patkar, William J Huth, 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: Nature immunology (Nat Immunol) Vol. 24 Issue 12 Pg. 2108-2120 (Dec 2023) ISSN: 1529-2916 [Electronic] United States
• PMID: 37932457 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

Chemical References

• Interleukin-27

Topics

• Mice
• Animals
• T-Lymphocytes, Regulatory
• Interleukin-27
• T-Lymphocytes, Helper-Inducer
• Immune Tolerance
• Immunity, Cellular
• Th17 Cells