Intestinal epithelial MHC-II is required for Th17 induction and epithelial antigen-presenting gene programs in the small intestine during EAE

The intestinal epithelium plays a critical role in immune microbiota interactions; however, its contribution to systemic autoimmunity remains incompletely understood. Here, we investigated the role of intestinal epithelial MHC class II (MHC II) in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. We generated mice with tamoxifen-inducible, intestinal epithelial cell (IEC) specific deletion of H2Ab1 (VillinCreERT2 H2Ab1flox/flox referred to as IEC MHCII ko) and induced EAE by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35_55). Littermate Cre-negative mice served as controls. To assess how epithelial MHCII affects intestinal immune and epithelial states during EAE, we performed 10x Genomics Chromium Single Cell Gene Expression Flex profiling of small intestinal cells from control EAE and IEC MHCII ko+EAE mice (n = 2 per group). These data indicate reduced accumulation of pathogenic Th17 cells in the small intestine of IEC MHCII ko+EAE mice and suggest that epithelial MHCII contributes to induction of inflammatory epithelial gene programs during EAE.