Role of Vitamin A in T Cell Homing to the Gut

Vitamin A supplementation significantly reduces infant mortality in developing countries, largely by reducing persistent diarrhea that is often aggravated by malnutrition. Vitamin A contributes to maintaining the integrity of mucosal epithelia and enhancing IgA responses in the gut. Recently, we found that vitamin A is essential for the homing of T cells to gut tissues. Retinoic acid (RA), an oxidative metabolite of retinol, even at 0.1 to 1 nM, enhances the expression of the gut-homing receptors, the integrin α4β7 and the chemokine receptor CCR9, on T cells upon activation in vitro, and grants them the capacity of migrating to the small intestine. The RA receptors RARα and/or β are involved in this effect. Dendritic cells of the gut-associated lymphoid organs, Peyer's patches and mesenteric lymph nodes, express the RAproducing enzymes, and can produce RA from retinol (vitamin A). Antigenic stimulation of T cells with these dendritic cells enhances α4β7 expression on T cells, depending on the production of RA by dendritic cells and its binding to RAR in T cells. Therefore, vitamin A-derived RA imprints T cells with the gut-homing specificity. Possible roles of this effect in the development of diseases and possible future treatments for them are discussed.