Abstract
It has long been recognized that vitamin A and its metabolites have immune-regulatory roles but the mechanism has been unclear. Recently, there has been a significant progress in elucidating the functions of retinoic acid in regulation of immune cell development. Retinoic acid (all-trans and 9-cis retinoic acid) is produced from the cells of the intestine such as dendritic cells and provides an intestine-specific environmental cue to differentiating immune cells. When T cells and B cells are activated in the intestine and associated-lymphoid tissues, gut homing receptors are induced on the cells in a retinoic acid and antigen-dependent manner. Retinoic acid, produced by gut dendritic cells, is also an important signal that induces IgA-producing B cells. The gut homing T cells and B cells play essential roles in protecting the digestive tract from pathogens. Retinoic acid is required also for production of mature phagocytes in bone marrow. On the other hand, retinoic acid induces a subset of FoxP3+ regulatory T cells which is important for maintaining immune tolerance in the gut. Therefore, retinoids provide both positive and negative regulatory signals to fine-control the mucosal immune system.
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