Hobit- and Blimp-1-driven CD4+ P2X7+ tissue resident memory T cells critically control chronic intestinal inflammation

Although tissue resident memory T (TRM) cells have been shown to regulate host protection in infectious disorders, their functional role in inflammatory bowel diseases (IBD) remains to be investigated. Here, we characterized TRM cells in human IBD and addressed their role in experimental models of intestinal inflammation with mice deficient for TRM-associated transcription factors and by TRM depletion. We show that pro-inflammatory TRM cells are increased in active IBD. Moreover, the presence of CD4+ but not CD8+ TRM cells in IBD patients predicts subsequent development of flares. In vivo, mice deficient in Hobit and Blimp-1 are protected from several models of colitis due to decreased pro-inflammatory cytokine secretion, impaired cytotoxicity and leukocyte chemotaxis. Finally, P2X7-induced TRM depletion via NAD enema leads to suppression of colitis activity. Taken together, our data argue for a central role of TRM cells in the pathogenesis of IBD and suggest that these cells are an interesting target for future therapeutic approaches. The 4 analyzed samples belong to 2 different groups with 2 biological replicates per group. One of the groups consisted of control samples.