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Melatonin synthesized by T lymphocytes as a ligand of the retinoic acid‐related orphan receptor
Author(s) -
Lardone Patricia J.,
Guerrero Juan M.,
FernándezSantos José M.,
Rubio Amalia,
MartínLacave Inés,
CarrilloVico Antonio
Publication year - 2011
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2011.00909.x
Subject(s) - melatonin , orphan receptor , retinoic acid , melatonin receptor , jurkat cells , immune system , nuclear receptor , receptor , biology , microbiology and biotechnology , rar related orphan receptor gamma , medicine , endocrinology , cancer research , immunology , foxp3 , t cell , biochemistry , cell culture , transcription factor , genetics , gene
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.