Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases

Figure 2

Role of RA in immune cells. RA can act on different cells of both the innate and adaptive immune systems exerting local action at mucosal sites and systemic action, which simultaneously, depending on where the RA-producing cells, mainly CD103⁺ DCs, are located when it releases the RA. (A) However, in an inflammatory environment (red box), PGE2 released during the inflammatory response inhibits the RALDH enzyme that is required for RA synthesis. When RA is released, it acts as follows: (B) RA together with proinflammatory cytokines contributes to the activation of DCs and the generation of effector T cells; (C) RA promotes macrophage modulation, inhibiting inflammatory mediators and the release of TNF and NO; (D) RA also activates ILC3, especially LTi cells, which are required for the formation of lymphoid tissue, including during fetal development; (E) RA induces expression of the molecules α4β7 and CCR9 in lymphocytes and ILCs and the homing of these cells into the intestine and promotes the balance of Th17/Treg cells in the GALT, assuring tolerance, but is also able to induce Th17 in the presence of infection and inflammation; and (F) RA promotes the activation of B cells and their differentiation into Ab-secreting plasma cells.