Vitamin A and immune regulation: role of retinoic acid in gut-associated dendritic cell education, immune protection and tolerance.

The vitamin A (VA) metabolite all-trans retinoic acid (RA) plays a key role in mucosal immune responses. RA is produced by gut-associated dendritic cells (DC) and is required for generating gut-tropic lymphocytes and IgA-antibody-secreting cells (IgA-ASC). Moreover, RA modulates Foxp3(+) regulatory T cell (T(REG)) and Th17 effector T cell differentiation. Thus, although RA could be used as an effective "mucosal adjuvant" in vaccines, it also appears to be required for establishing intestinal immune tolerance. Here we discuss the roles proposed for RA in shaping intestinal immune responses and tolerance at the gut mucosal interface. We also focus on recent data exploring the mechanisms by which gut-associated DC acquire RA-producing capacity.