Abstract
Persistent diarrhea is a major cause of infant deaths in developing countries. Vitamin A supplementation significantly reduces the severity of diarrhea and the mortality. The vitamin A metabolite retinoic acid (RA) is an essential factor to imprint gut-homing specificity on lymphocytes. Indeed, vitamin A deficiency causes the depletion of lymphocytes from the small intestinal lamina propria. The gut-related lymphoid organs and the small intestinal lamina propria consist of dendritic cells (DCs) capable of producing RA. RA also contributes to the immune regulation and tolerance by enhancing the transforming growth factor-β-dependent differentiation of inducible Foxp3^+ regulatory T cells and inhibiting that of inflammatory Th17 cells. Thus, the regulation of RA production by gut DCs is critical for immune regulation as well, and mainly depends on ALDH1A2 expression. Its expression is induced mainly by granulocyte-macrophage colony-stimulating factor and other factors constitutively present or induced in the intestinal microenvironment.
