Researchers at UT Southwestern Medical Center in Dallas have identified a specific biological mechanism through which gut bacteria influence the development of the immune system. The findings, published in the journal Cell Host & Microbe, describe a previously unknown cellular network that transports vitamin A to T cells, a critical class of immune cells responsible for protecting the body against infection.
The study, led by first author Tarun Srinivasan, a third-year medical student in the Perot Family Scholars Medical Scientist Training Program, clarifies the connection between the gut microbiome and vitamin A, both of which are known to be essential for immune health. While the individual importance of these factors was established, the method by which they interact remained unclear until this research.
Using mouse models, the team observed that gut bacteria trigger a stepwise transfer of vitamin A between cells. The process initiates in the intestinal lining, where microbial presence stimulates intestinal epithelial cells to produce serum amyloid A, a protein that binds to vitamin A. This protein then delivers the nutrient to immune cells within the intestine. These immune cells subsequently transport the vitamin A to nearby lymph nodes, where they pass vitamin A-derived signals to developing T cells.
Co-corresponding authors Lora Hooper, Chair and Professor of Immunology, and Andrew Koh, Professor of Pediatrics and Chief of the Division of Pediatric Hematology and Oncology, both members of the Harold C. Simmons Comprehensive Cancer Center, noted that the removal of gut bacteria effectively shuts down this delivery system. Without this microbial input, developing T cells fail to mature properly or migrate to the intestine, impairing the body’s ability to maintain normal immune balance or respond to infections.
The researchers further observed that this pathway becomes increasingly active during early life, a period when the immune system is initially programmed. This suggests that disruptions to the microbiome during this critical window could have lasting consequences for immune function. The authors propose that these findings may help explain how antibiotic exposure during early life influences immune development, as such treatments can interfere with the microbial signals required for this nutrient pathway.
