A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice.

Autor: Hackstein CP; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Costigan D; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Drexhage L; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Pearson C; Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK., Bullers S; Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK., Ilott N; Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK., Akther HD; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Gu Y; Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK., FitzPatrick MEB; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Harrison OJ; Center for Fundamental Immunology, Benaroya Research Institute, 1201 9th Ave, Seattle, WA, 98101, USA.; Department of Immunology, University of Washington, 750 Republican St, Seattle, WA, 98108, USA., Garner LC; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Mann EH; Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK., Pandey S; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Friedrich M; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK., Provine NM; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Uhlig HH; Translational Gastroenterology Unit, and Biomedical Research Centre, and Department of Paediatrics, University of Oxford, Oxford, OX39DU, UK., Marchi E; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Powrie F; Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK., Klenerman P; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK. paul.klenerman@ndm.ox.ac.uk.; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK. paul.klenerman@ndm.ox.ac.uk., Thornton EE; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. emily.thornton@imm.ox.ac.uk.; Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK. emily.thornton@imm.ox.ac.uk.; Nuffield Department of Medicine, University of Oxford, Oxford, UK. emily.thornton@imm.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Dec 03; Vol. 13 (1), pp. 7472. Date of Electronic Publication: 2022 Dec 03.
DOI: 10.1038/s41467-022-35126-3
Abstrakt: Interactions with commensal microbes shape host immunity on multiple levels and play a pivotal role in human health and disease. Tissue-dwelling, antigen-specific T cells are poised to respond to local insults, making their phenotype important in the relationship between host and microbes. Here we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics associated with innate-like T cells. This cell population is abundant and conserved in the human and murine colon and endowed with polyfunctional effector properties spanning classic Th1- and Th17-cytokines, cytotoxic molecules, and regulators of epithelial homeostasis. T cells with this phenotype are increased in ulcerative colitis patients, and their presence aggravates pathology in dextran sodium sulphate-treated mice, pointing towards a pathogenic role in colitis. Our findings add to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu.
(© 2022. The Author(s).)
Databáze: MEDLINE
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