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In Mouse Study, NIH Investigators Observe the Immune-Boosting Properties of Vitamin A

A new study led by Dr. Yasmine Belkaid and colleagues in NIAID's 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.

Photo of three carrots arranged in the shape of an ‘A'
Credit: NIAID

Background

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.

Results of Study

In this latest study, Belkaid's lab collaborated with Dr. Pamela Schwartzberg of the National Human Genome Research Institute's 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.

Crystal structure of retinoic acid receptor alpha (ribbon diagram)
Crystal structure of retinoic acid receptor alpha (ribbon diagram)
Reference: Protein Data Bank, DOI: 10.2210/pdb3nsp/pdb
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 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.

Significance

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 (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.

Next Steps

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.

More Information

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 page

Dr. Schwartzberg's lab page

WHO Vitamin A deficiency Web page

Last Updated January 03, 2012

Last Reviewed June 14, 2011