Identification of a unique subset of tissue-resident memory CD4+ T cells in Crohn’s disease

The impact of tissue-resident memory T cells (Trm) on the pathogenesis of inflammatory bowel disease remains controversial due to their heterogeneity. In particular, the pathological function of CD4+Trm, as opposed to their CD8+counterparts, is largely unknown. Here, using a comprehensive analytical approach, we found that CD103+CD4+Trm with an inflammatory phenotype were increased in the gut of Crohn’s disease (CD) patients but not in ulcerative colitis patients. Further profiling revealed that a subset of CD103+CD4+Trm, expressing CD161 and CCR5, were specific to CD patients and that this subset exerted cytotoxic activity. CD103+CD161+CCR5+CD4+Trm were predominant producers of proinflammatory cytokines, highlighting the importance of this specific subset in the pathogenesis of CD.