Year: 2025
Type: article
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)
Source: The Journal of Immunology
Authors: Tarun Srinivasan, Chaitanya Dende, Lora Hooper
Institution: The University of Texas Southwestern Medical Center
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416447378
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