Figure 1.

Regulation of T cells and B cells by RAs. T cells and B cells express RARs and are major targets of RA regulation. RAs and their receptors appear to regulate T and B cells through genomic and non-genomic functions. RAs affect the effector function, gut-homing receptor expression, and apoptosis of CD4⁺ T cells. In the intestine, RAs promote gut-homing effector T cells (Th1 and Th17) and Tregs. Regulation of T cells by RAs occurs at the time of antigen priming, and DCs express RA-producing RALDH2. Moreover, RAs induce co-stimulatory receptors and RALDH2 in DCs. Therefore, DCs and other antigen presenting cells play central roles in regulating T cells by activating lymphocytes and producing RAs. RAs also induce the expression of P2X7 and Art2b on T cells to induce apoptosis caused by inflammatory mediators such as NAD and ATP, which are typically leaked out of dying cells in inflammatory conditions. This function of RAs induces effector T cell contraction in the intestines. RAs also induce gut-homing IgA-producing B-1 and B-2 cells in gut-associated lymphoid tissues. However, RAs function to suppress IgE production. RAs promote IL-10-producing regulatory T and B cells. The arrows indicate either positive (↑) or negative (↓) effect of RAs.

RXR, retinoid X receptor; ULK1, UNC51-like kinase-1; IRF4, interferon regulatory factor 4.