Fig. 6: Indirect effects of retinoic acid on T lymphocytes to stimulate IgA class switch recombination.
From: The role of retinoic acid in the production of immunoglobulin A
Epithelial cells metabolize dietary vitamin A into retinoic acid (RA), which is required for dendritic cells (DCs) to differentiate into RA-producing DCs. Within Peyer’s patches (PPs), RA secretion affects the differentiation of CD4 + T cells, thereby facilitating IgA class switching by B lymphocytes. In particular, RA regulates the balance of regulatory T cell (Treg) and T helper 17 (Th17)-cell differentiation. RA suppresses the production of interleukin-4 (IL4), interleukin-21 (IL21) and interferon-ƴ (IFNƴ), which are cytokines that inhibit Treg formation, by T cells. As such, RA indirectly promotes the differentiation of Tregs. Tregs themselves are involved in the induction of antigen-independent IgA differentiation by secreting TGFβ. Moreover, Tregs can differentiate into T follicular helper cells (Tfhs), which are involved in antigen-dependent IgA production by secreting IL21 within PPs. RA also promotes the differentiation of T-helper 2 cells, which secrete interleukin-5 and, together with IL21, promote an IgA-inducing environment.
