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

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Abstract
Interactions with commensal microbes shape host immunity on multiple levels and are recognized to play a pivotal role in human health and disease. In this study, we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics typically associated with innate-like T cells, including the expression of the key transcription factor PLZF and the ability to respond to cytokines including IL-12, IL-18 and IL-23 in a TCR-independent manner. These M HC-II restricted, i nnate-like, c ommensal-reactive T cells (T MIC ) are endowed with a polyfunctional effector potential spanning classic Th1- and Th17-cytokines, cytotoxic molecules as well as regulators of epithelial homeostasis and represent an abundant and conserved cell population in the human and murine colon. T cells with the T MIC phenotype were increased in ulcerative colitis patients and their presence aggravated pathology in DSS-treated mice, pointing towards a pathogenic role in colitis. Our findings add T MIC cells 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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