Dietary fiber and Segmented Filamentous Bacteria interaction with intestinal epithelial cells supports the development of CD4 +CD8αα +intraepithelial T cells

Abstract Double positive intraepithelial lymphocytes (DP IELs) are microbiome induced CD4 +CD8αα +T cells that play a role in maintaining homeostasis and reducing inflammation the small intestine. While impact of on intestinal immune system has been extensively studied, little is known about how changes macronutrients, such as dietary fiber, affect development important cell populations through microbiome. Here we show diet low fermentable fiber (LFF) impairs DP IELs by MHC-II expression epithelial (IECs). Bulk RNA sequencing ileal IECs revealed LFF fed mice had lower genes associated with antigen presentation machinery. Subsequently, flow cytometry analysis confirmed increased standard chow mice, which required for IEL development. 16s rRNA microbiota showed SFB reduced these animals. We found colonizing induces restores fiber-dependent manner. Finally, using offspring naturally harbor SFB, IFN-γ levels ileum increase gradually over time correlate colonization. These results suggest supporting colonization increasing cells. Supported grants from NIH (1R011DK129950) startup funds Emory University