Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of T H 17 cell immunity.

Autor: Lin CH; School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA., Wu CJ; School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA., Cho S; School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA., Patkar R; School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA., Huth WJ; School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA., Lin LL; School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA., Chen MC; School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA., Israelsson E; Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Betts J; Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Niedzielska M; Bioscience, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Patel SA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA., Duong HG; Department of Medicine, University of California, San Diego, La Jolla, CA, USA., Gerner RR; Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA., Hsu CY; Department of Pathology, University of California San Diego, La Jolla, CA, USA., Catley M; Bioscience, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Maciewicz RA; Bioscience, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Chu H; Department of Pathology, University of California San Diego, La Jolla, CA, USA.; UC San Diego Center for Mucosal Immunology, Allergy, and Vaccines, Chiba University, La Jolla, CA, USA.; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA., Raffatellu M; Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.; UC San Diego Center for Mucosal Immunology, Allergy, and Vaccines, Chiba University, La Jolla, CA, USA.; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA., Chang JT; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.; Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA., Lu LF; School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA. lifanlu@ucsd.edu.; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA. lifanlu@ucsd.edu.; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA. lifanlu@ucsd.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2023 Dec; Vol. 24 (12), pp. 2108-2120. Date of Electronic Publication: 2023 Nov 06.
DOI: 10.1038/s41590-023-01667-y
Abstrakt: Regulatory T cells (T reg cells) are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which T reg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying T reg cells from different tissue origins under systemic autoimmunity, in the present study we show that interleukin (IL)-27 is specifically produced by intestinal T reg cells to regulate helper T17 cell (T H 17 cell) immunity. Selectively increased intestinal T H 17 cell responses in mice with T reg 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 + CD62L lo T reg cell subset that is distinct from previously characterized intestinal T reg cell populations as the main IL-27 producers. Collectively, our study uncovers a new T reg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue and provides further mechanistic insights into tissue-specific T reg cell-mediated immune regulation.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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