Retinoic acid production by intestinal dendritic cells

Subpopulations of dendritic cells (DCs) in the small intestine and its related lymphoid organs can produce retinoic acid (RA) from vitamin A (retinol). Through the RA production, these DCs play a pivotal role in imprinting lymphocytes with gut-homing specificity, and contribute to the development of immune tolerance by enhancing the differentiation of Foxp3(+) regulatory T cells and inhibiting that of inflammatory Th17 cells. The RA-producing capacity in these DCs mostly depends on the expression of retinal dehydrogenase 2 (RALDH2, ALDH1A2). It is likely that the RALDH2 expression is induced in DCs by the microenvironmental factors in the small intestine and its related lymphoid organs. The major factor responsible for the RALDH2 expression appears to be GM-CSF. RA itself is essential for the GM-CSF-induced RALDH2 expression. IL-4 and IL-13 also enhance RALDH2 expression, but are dispensable. Toll-like receptor-mediated signals can also enhance the GM-CSF-induced RALDH2 expression in immature DCs.