title: The differential characterization of GPR55 receptor in human peripheral blood reveals a distinctive expression in monocytes and NK cells and a proinflammatory role in these innate cells.
abstract: G protein-coupled receptor 55 (GPR55) is activated by endogenous, plant-derived and synthetic cannabinoids. Recent studies reported a broad tissue distribution for GPR55 and found prominent roles for this receptor in inflammatory pain, gut and bone physiology, as well as cancer. However, little is known about the expression and function of GPR55 in immune cells. To address this question, we performed a detailed characterization of GPR55 in different human innate and adaptive immune populations using polychromatic flow cytometry and we found that monocytes and NK cells expressed remarkable levels of this receptor compared to several cells of adaptive immunity. GPR55 activation by the specific agonist O-1602 boosted IL-12 and TNF-α production, and decreased endocytic activity, in LPS-activated monocytes. In addition, it increased CD69 activation marker expression, granzyme B and CD107a-dependent cytotoxicity and IFN-γ and TNF-α production in NK cells activated by both IL-2 and IL-12. These over-stimulatory effects of GPR55 were antagonized by its selective antagonist cannabidiol. Altogether, our data thus unveil a proinflammatory role for GPR55 in innate immunity that may be important for the design of new immune therapeutic strategies.
authors.affiliation: European Center for Brain Research (CERC), I.R.C.C.S. Santa Lucia Foundation, via del Fosso di Fiorano 64, 00143 Rome, Italy Faculty of Veterinary Medicine, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy v.chiurchiu@hsantalucia.it.
authors.forename: Valerio
authors.initials: V
authors.lastname: Chiurchiù
authors.affiliation: European Center for Brain Research (CERC), I.R.C.C.S. Santa Lucia Foundation, via del Fosso di Fiorano 64, 00143 Rome, Italy Faculty of Veterinary Medicine, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Lanuti
authors.affiliation: European Center for Brain Research (CERC), I.R.C.C.S. Santa Lucia Foundation, via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Bardi
authors.affiliation: European Center for Brain Research (CERC), I.R.C.C.S. Santa Lucia Foundation, via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Battistini
authors.affiliation: European Center for Brain Research (CERC), I.R.C.C.S. Santa Lucia Foundation, via del Fosso di Fiorano 64, 00143 Rome, Italy Center of Integrated Research, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D001775:Blood Circulation; D002185:Cannabidiol / Q000494:pharmacology / Q000031:analogs & derivatives; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002478:Cells, Cultured; D003510:Cyclohexanes / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D003510:Cyclohexanes; D016207:Cytokines; C524885:GPR55 protein, human; D008070:Lipopolysaccharides; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled; D012118:Resorcinols; D002185:Cannabidiol; C568537:O-1602 compound
keywords: cannabinoid receptors; immunoregulation; innate immunity