Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 12/19/2011
Publication Date: 9/10/2012
Citation: Stephensen, C.B. 2012. Vitamin A and immune function. In: Preedy, V.R., editor. Food and Nutritional Components in Focus No. 1: Vitamin A and Carotenoids: Chemistry, Analysis, Function and Effects. Cambridge, UK: Royal Society of Chemistry. p. 501-515. DOI:10.1039/ISBN
Interpretive Summary: Vitamin A is an essential nutrient that was first identified because it causes night blindness. Eventually it was realized that vitamin A deficiency also impairs immune function and thus increases the risk of infectious diseases. Work over the last twenty years has identified specific mechanisms by which vitamin A affects immune function. These studies, largely conducted in experimental animal models, show that vitamin A is essential for development of cells of the innate immune system, such as macrophages and neutrophils, which develop in the bone marrow and have a primary role of ingesting and killing invading microorganisms. In addition, vitamin A deficiency impairs adaptive immunity, which results in immunologic memory and occurs after infections or immunizations. Specifically, vitamin A deficiency alters the development of memory T lymphocytes, which can alter the type of protective immunity that develops. For example, vitamin A deficiency impairs the adaptive immune response to mucosal infections such as diarrheal pathogens or intestinal parasites. In summary, vitamin A deficiency impairs immune function and thereby increases the risk of death from infectious diseases.
Technical Abstract: Vitamin A deficiency increases the risk of death from infectious diseases in infants and young children in areas of the world where vitamin A deficiency is common. This increased risk apparently results from impaired innate and adaptive immune function. Retinoic acid is the major metabolite of vitamin A produced by immune cells. In particular, dendritic cells produce retinoic acid that acts to regulate gene expression in cells of the immune system. Innate immune cells, such as neutrophils, develop in the bone marrow in response to locally produced retinoic acid. Neutrophil function is impaired by vitamin A deficiency in that their ability to kill bacteria is compromised, thus increasing the risk of invasive bacterial infections. Natural Killer (NK) cells are active against viruses and other intracellular bacteria and their numbers and activity are decreased by vitamin A deficiency. Antigen-presenting cells, particularly intestinal dendritic cells, produce retinoic acid and thereby regulate the development of both B and T lymphocytes, the major effector cells of adaptive immunity. In particular, retinoic acid enhances the development of some T helper (Th) cell phenotypes, including Th2 cells and inducible T regulatory (iTreg) cells, regulates the development of B cells that produce antibodies such as immunoglobulin A (IgA), and promotes trafficking of lymphocytes to the intestine and other mucosal sites by inducing expression of chemokine receptor 9 and a4ß7 integrin. Retinoic acid thus is particularly active in boosting mucosal immunity and vitamin A deficiency thus particularly impairs protection against mucosal infections, such as diarrheal pathogens.