title: Melatonin synthesized by T lymphocytes as a ligand of the retinoic acid-related orphan receptor.
abstract: Melatonin modulates a wide array of physiological events with pleiotropic effects on the immune system. While the relevance of specific melatonin membrane receptors has been well established for several biological functions, retinoic acid-related orphan receptor alpha (RORα) has been suggested as a mediator of nuclear melatonin signalling by results obtained from pharmacological approaches. However, a melatonin-mediated downstream effect cannot be ruled out, and further evidence is needed to support a direct interaction between melatonin and RORα. Here, we show that RORα is mainly located in human Jurkat T-cell nucleus, and it is co-immunoprecipitated with melatonin. Moreover, immunocytochemistry studies confirmed the co-localization of melatonin and RORα. Melatonin promoted a time-dependent decrease in nuclear RORα levels, suggesting a role in the RORα transcriptional activity. Interestingly, RORα acts as a molecular switch implicated in the mutually exclusive generation of Th17 and Treg cells, both involved in the harm/protection balance of immune conditions such as autoimmunity or acute transplant rejection. Therefore, the identification of melatonin as a natural modulator of RORα gives it a tremendous therapeutic potential for a variety of clinical disorders.
authors: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, Seville, Spain.
authors: Patricia J
authors: PJ
authors: Lardone
authors: Juan M
authors: JM
authors: Guerrero
authors: José M
authors: JM
authors: Fernández-Santos
authors: Amalia
authors: A
authors: Rubio
authors: Inés
authors: I
authors: Martín-Lacave
authors: Antonio
authors: A
authors: Carrillo-Vico
mesh_terms: D015153:Blotting, Western; D006801:Humans; D047468:Immunoprecipitation; D019169:Jurkat Cells; D008550:Melatonin / Q000378:metabolism*; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D008550:Melatonin