Scientists at UT Southwestern Medical Center have identified a mechanism by which gut bacteria assist in regulating the immune system by directing the flow of vitamin A to specific immune cells. The findings, published in the journal Cell Host & Microbe, describe a previously unknown cellular network that links microbial activity to immune development.
The research indicates that gut bacteria trigger a stepwise transfer of vitamin A between cells. This process starts in the intestinal lining, where microbes stimulate the production of a protein called serum amyloid A. This protein binds to vitamin A and delivers it to immune cells within the intestine. These immune cells then transport the vitamin A to nearby lymph nodes, where they pass vitamin A-derived signals to developing T cells.
T cells are a class of immune cells responsible for protecting the body from infection. The study notes that the immune system relies on signals derived from vitamin A to guide the development of these cells. While the importance of both gut microbes and vitamin A for a healthy immune system has been recognized for years, the specific connection between them was not understood until now.
When researchers removed gut bacteria from mice in the study, the vitamin A delivery system was largely shut down. As a result, developing T cells were unable to mature properly or migrate to the intestine. The researchers stated that because these steps are essential for building a functional immune defense, disruptions in this pathway could impair the body's ability to respond to infections or maintain normal immune balance.
The study also showed that this pathway becomes increasingly active during early life, a critical period when the immune system is being programmed. The authors suggested that interruptions during this window could have lasting consequences. They noted the findings may help explain how antibiotic exposure during early life influences immune development, as the pathway depends on signals from gut microbes.
The work was led by first author Tarun Srinivasan, a third-year medical student in UT Southwestern's Perot Family Scholars Medical Scientist Training Program. Co-corresponding authors include Lora Hooper, chair and professor of immunology, and Andrew Koh, professor of pediatrics and chief of the Division of Pediatric Hematology and Oncology. Both are members of the Harold C. Simmons Comprehensive Cancer Center.
