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

Abstract

Although tissue-resident memory T cells (T_RM cells) have been shown to regulate host protection in infectious disorders, their function in inflammatory bowel disease (IBD) remains to be investigated. Here we characterized T_RM cells in human IBD and in experimental models of intestinal inflammation. Pro-inflammatory T_RM cells accumulated in the mucosa of patients with IBD, and the presence of CD4⁺CD69⁺CD103⁺ T_RM cells was predictive of the development of flares. In vivo, functional impairment of T_RM cells in mice with double knockout of the T_RM-cell-associated transcription factors Hobit and Blimp-1 attenuated disease in several models of colitis, due to impaired cross-talk between the adaptive and innate immune system. Finally, depletion of T_RM cells led to a suppression of colitis activity. Together, our data demonstrate a central role for T_RM cells in the pathogenesis of chronic intestinal inflammation and suggest that these cells could be targets for future therapeutic approaches in IBD.