The Gut Microbiota Regulates Intestinal Retinoid Flux to Promote Adaptive Immunity 2348

Abstract Description The intestinal microbiota plays a critical role in shaping the adaptive immune system within the small intestine, but the mechanisms remain unclear. Here, we show that the commensal microbiota regulates intestinal T cell function by controlling vitamin A flux to developing T cells. Our findings reveal that the microbiota initiates a stepwise transfer of dietary retinoids, driving their movement from intestinal epithelial cells to migratory myeloid cells, and ultimately to developing T cells in the mesenteric lymph nodes (mLNs). This process is driven by microbiota-induced epithelial expression of serum amyloid A proteins (SAAs), which facilitate retinoid transport along the epithelial–myeloid cell–T cell axis. These retinoids promote sequential activation of retinoic acid receptors (RARs) across a myeloid-T cell axis culminating in an RAR-dependent transcriptional program that promotes T cell homing to the small intestine. This microbially regulated retinoid flux is essential during postnatal development, enabling T cell migration from the mLNs to the small intestine as microbial colonization expands post-weaning. Our results uncover a microbiota-driven mechanism linking dietary retinoid flux to T cell trafficking during early development. Funding Sources NIH/NIDDK R01 DK070855 NIH T32 AI007520 Howard Hughes Medical Institute Topic Categories Mucosal and Regional Immunology (MUC)