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

Carl-Philipp Hackstein, Dana Costigan, Linnea Drexhage, Claire Pearson, Samuel Bullers, Nicholas Ilott, Hossain Delowar Akther, Yisu Gu, Michael E. B. FitzPatrick, Oliver J. Harrison, Lucy C. Garner, Elizabeth H. Mann, Sumeet Pandey, Matthias Friedrich, Nicholas M. Provine, Holm H. Uhlig, Emanuele Marchi, Fiona Powrie, Paul Klenerman () and Emily E. Thornton ()
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Carl-Philipp Hackstein: University of Oxford
Dana Costigan: University of Oxford
Linnea Drexhage: University of Oxford
Claire Pearson: University of Oxford
Samuel Bullers: University of Oxford
Nicholas Ilott: University of Oxford
Hossain Delowar Akther: University of Oxford
Yisu Gu: University of Oxford
Michael E. B. FitzPatrick: University of Oxford
Oliver J. Harrison: Benaroya Research Institute
Lucy C. Garner: University of Oxford
Elizabeth H. Mann: University of Oxford
Sumeet Pandey: University of Oxford
Matthias Friedrich: University of Oxford
Nicholas M. Provine: University of Oxford
Holm H. Uhlig: University of Oxford
Emanuele Marchi: University of Oxford
Fiona Powrie: University of Oxford
Paul Klenerman: University of Oxford
Emily E. Thornton: University of Oxford

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-35126-3

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