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Hackstein, Carl-Philipp; Costigan, Dana; Drexhage, Linnea; Pearson, Claire; Bullers, Samuel; Ilott, Nicholas; Akther, Hossain Delowar; Gu, Yisu; FitzPatrick, Michael E B; Harrison, Oliver J; Garner, Lucy C; Mann, Elizabeth H; Pandey, Sumeet; Friedrich, Matthias; Provine, Nicholas M; Uhlig, Holm H; Marchi, Emanuele; Powrie, Fiona; Klenerman, Paul; Thornton, Emily E
Nature communications, 12/2022, Volume: 13, Issue: 1Journal Article
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.
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