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).
About The Expert
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
Emily E Thornton
References
PubMed