A study led by Dr. Yasmine Belkaid and colleagues in the NIAID Laboratory of Parasitic Diseases helps shed light on how vitamin A regulates the immune system at mucosal surfaces—the moist linings of the mouth, lungs, and gastrointestinal (GI) tract. The study, published in the March 2011 issue of Immunity, demonstrates in mice that certain immune T cells use vitamin A metabolites to help maintain the health of the host.
Vitamin A is found in foods such as carrots, spinach, and sweet potatoes. When the body breaks down vitamin A, a key product is retinoic acid, which is needed for growth, development, and immunity.
The GI tract often is where the immune system first comes in contact with proteins and microorganisms and receives signals that indicate whether a substance is harmful or helpful.
Previously, Belkaid's group demonstrated that retinoic acid cues T cells in the gut to differentiate into cells that, when needed, help maintain immune tolerance. Without this brake on the immune response, immune cells can attack helpful bacteria naturally found in the gut, harmless proteins in food, or even the body's own cells, resulting in conditions like autoimmune diseases and allergies.
In this latest study, Belkaid's lab collaborated with Dr. Pamela Schwartzberg of the National Human Genome Research Institute, Genetic Disease Research Branch, to examine the role of retinoic acid in the immune response to a disease-causing parasite and to vaccination. The investigators examined four groups of mice: 1) one receiving a diet lacking vitamin A; 2) one receiving a similar diet, but with sufficient vitamin A; 3) one with a receptor for retinoic acid; and 4) one without this receptor.
The vitamin A-deficient mice were able to clear infection and mount an appropriate immune response to vaccination after receiving retinoic acid, demonstrating that the deficiency is easily reversible. Importantly, the National Institutes of Health (NIH) team also found that retinoic acid played a direct role in the early response of T cells, providing the fuel necessary for T cells to protect mucosal surfaces against infection and foster immunosurveillance, the monitoring of the immune system to recognize and destroy harmful cells.
The results of the new study and Dr. Belkaid's previous work suggest that vitamin A is a strong regulator of the immune response in the gut, helping adjust the response to appropriately handle encounters with both helpful and harmful substances.
What is clear is that proper amounts of vitamin A play an important role in human health. The World Health Organization estimates that approximately 250 million preschool children are deficient in vitamin A, which is associated with increased susceptibility to diarrheal disease and poorer response to vaccination. NIH-supported studies that explore the interplay between the immune system and dietary nutrients help broaden understanding of mucosal immunity and provide insight into how the balance between immune tolerance and response in the gut is maintained.
The study adds to the evidence suggesting that vitamin A metabolism helps T cells in the GI tract respond appropriately to both beneficial and harmful challenges. While the new data show that mice need retinoic acid to carry out this role, additional studies are needed to determine if the same is true in humans.
Hall JA, Cannons JL, Grainger JR, Dos Santos LM, Hand TW, Naik S, Wohlfert EA, Chou DB, Oldenhove G, Robinson M, Grigg ME, Kastenmayer R, Schwartzberg PL, Belkaid Y. Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity. 2011 Mar 25;34(3):435-47.
Dr. Belkaid's Lab
Dr. Schwartzberg's Lab
WHO Vitamin A Deficiency Web Page
Last Updated January 03, 2012