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

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.