Epithelial cells program adaptive immunity through antigen compartmentalization

Major histocompatibility complex class II (MHCII) expression on IECs has been proposed to contribute to antigen presentation and T cell priming during intestinal infection, but the cell type-specific transcriptional programs influenced by epithelial MHCII remain unclear.

Here, we performed single-cell RNA sequencing (10x Genomics) to comprehensively profile intestinal epithelial and immune cell populations during Citrobacter rodentium infection. We analyzed colonic tissues from H2-Ab1^fl/fl (wild-type) and H2-Ab1^Villin (IEC-specific conditional knockout) mice at naïve baseline and days 9, 14, and 42 post-infection, capturing acute infection, peak response, and memory phases. This dataset enables dissection of MHCII-dependent and -independent transcriptional responses across diverse epithelial lineages and immune cell subsets, providing insights into how IEC-intrinsic MHCII expression shapes mucosal immunity and tissue-resident memory formation during bacterial infection.