Colonocytes targeted by Citrobacter rodentium elicit epithelial MHCII-restricted help from CD4 T cells 2044

Abstract Description IL-22+ CD4 T cells play a key role in intestinal defense against the murine pathogen Citrobacter rodentium (C.r), yet the direct interactions between T cells and intestinal epithelial cells (IECs) remains unclear. Our study shows a significant increase in MHCII+ IECs during C.r infection, peaking during the adaptive immune response. In IEC-specific MHCII-deficient (H2Ab1Villin) mice, we observed crypt invasion, absence of STAT3 activation (downstream signaling pathway for IL-22), and reduced effector CD4 T cell populations, which correlated with increased C.r levels in feces and liver. Post-clearance of C.r, we observed a reduction in CD69+CD103+ and CD69+CD103– tissue-resident memory (TRM) CD4 T cells. To explore the role of epithelial MHCII in antigen-specific T cell responses, we generated epitope-tagged C.r to track CD4 T cell activation in vivo. Targeting the LCMV gp66 epitope downstream of the espZ virulence gene revealed fewer IL-22+ SMARTA CD4 T cells in the colon of C.r-gp66-infected H2Ab1Villin mice compared to controls, with a reciprocal increase in colon-draining lymph nodes. Surprisingly, antigens secreted into the IEC cytosol elicited a higher production of tissue-resident effector T cells compared to bacterial or membrane-bound antigens. These findings uncover a novel role for IEC-derived MHCII and IEC-accessible antigens in the colonic retention of both effector and TRM CD4 T cells, highlighting their importance in optimal defense against enteric infections. Funding Sources Supported by R37AI169864, F30DK135345, T32AI007051, and T32GM008361. Topic Categories Mucosal and Regional Immunology (MUC)