A new study in which National Human Genome Research Institute researchers collaborated with colleagues from the National Institute of Allergy and Infectious Disease 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 respond to infection or vaccination and maintain the health of the host. Often the GI tract 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. 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.
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. 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, Yasmine Belkaid, Ph.D., and colleagues in NIAID's Laboratory of Parasitic Diseases collaborated with Pamela Schwartzberg, M.D., Ph.D. and Jennifer Cannons, Ph.D., of NHGRI's Genetic Disease Research Branch to examine the role of retinoic acid in the immune response to a disease-causing parasite and vaccination. The investigators examined four groups of mice: those given nearly identical diets, except one group received food lacking vitamin A and the other group received food with sufficient vitamin A, and mice with and without a receptor for retinoic acid. Mice fed vitamin A-deficient diets or mice lacking the retinoic acid receptor did not mount a robust T-cell response to infection or vaccination. Mice without vitamin A deficiency and with the retinoic acid receptor cleared the infection and responded to the vaccine.
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 readily reversible. Importantly, the NIH team also found that retinoic acid played a direct role in the early response of T cells, providing fuel necessary for T cells to protect mucosal surfaces against infection and foster immunosurveillance.
Taken together, the results of the new study and 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. 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.
What is clear is that proper amounts of vitamin A play an important role in human health. The World Health Organization (WHO) 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.
To read the study, go to: Essential Role for Retinoic Acid in the Promotion of CD4+ T Cell Effector Responses via Retinoic Acid Receptor Alpha
More information on what the WHO is doing to combat vitamin A deficiency can be found at: www.who.int/nutrition/topics/vad/en.
Information on the research in Dr. Schwartzberg's lab can be found at: www.genome.gov/Staff/Schwartzberg.
Information on the research in Dr. Belkaid's lab can be found at: www.niaid.nih.gov/labsandresources/labs/aboutlabs/lpd/mucosalimmunology/Pages/belkaid.aspx.
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Last Reviewed: March 25, 2014