Retinoic acids regulate apoptosis of T lymphocytes through an interplay between RAR and RXR receptors.
Vitamin A deficiency has been known for a long time to be accompanied with immune deficiency and susceptibility to a wide range of infectious diseases. Increasing evidence suggests that retinoic acids derived from vitamin A are involved in the functional regulation of the immune system. Of the two groups of retinoid receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs) all-trans and 9-cis retinoic acids are high affinity ligands for RARs and 9-cis retinoic acid additionally binds to RXRs. In cells, at high concentrations, all-trans retinoic acid can be converted to 9-cis retinoic acid by unknown mechanisms. Apoptosis plays a major role in shaping the T cell repertoire and one way in which retinoids may affect immune functions is to influence the various apoptosis pathways. Indeed, it has been shown that retinoic acids can induce apoptosis, increase the rate of dexamethasone-induced death and inhibit activation-induced death of thymocytes and T lymphocytes. Therefore, retinoids together with glucocorticoids may be involved in regulating positive and negative selection of T lymphocytes. Here we demonstrate that retinoids can induce apoptosis of T cells through the stimulation of RARgamma. Specific stimulation of RARalpha, on the other hand, prevents both RARgamma-dependent and TCR-mediated cell death. In all these functions 9-cis retinoic acid proved to be more effective than all-trans retinoic acid suggesting the involvement of RXRs. Based on these results a possible mechanism through which costimulation of RARs and RXRs might affect spontaneous and activation-induced death of T lymphocytes is proposed.
Szondy
Z
Z
Department of Biochemistry, University Medical School of Debrecen, Hungary, H-4012. szondy@indi.dote.hu
Reichert
U
U
Fésüs
L
L
D017209:Apoptosis / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology*; D014212:Tretinoin / Q000502:physiology*
D018168:Receptors, Retinoic Acid; D014212:Tretinoin