Effects of Retinoids at the Systemic Level

All-trans-retinoic acid (ATRA) exerts many effects by stimulation of RA receptors, while 9-cis RA, another isomer, may also stimulate the retinoid X receptors (RXRs). In steady-state conditions, RA is released from the dendritic cells (DC) in the intestines and induces tolerance at the mucosal surfaces due to enhancement of tolerogenic DC and T regulatory cells. In B cells, the central immune regulatory role of RA is related to immunoglobulin class switching. RA is necessary to the embryonic and fetal cardiovascular development, including differentiation into adult cardiac muscle. RA regulates the expression of several genes inducing the production of many proteins in the heart. RA may also play a physiologic role in the development of the blood-brain barrier. RA, in pharmacologic concentrations, is capable of inducing tight junction expression in endothelial cells of the human brain, producing pluripotent stem cells and stimulating the RXR pathway.