1. Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of TH17 cell immunity
- Author
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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, and Lu, Li-Fan
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Autoimmune Disease ,Digestive Diseases ,Inflammatory Bowel Disease ,Aetiology ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Underpinning research ,Inflammatory and immune system ,Mice ,Animals ,T-Lymphocytes ,Regulatory ,Interleukin-27 ,T-Lymphocytes ,Helper-Inducer ,Immune Tolerance ,Immunity ,Cellular ,Th17 Cells ,Biochemistry and cell biology - 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.
- Published
- 2023