title: The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells.
abstract: Natural killer (NK) cells possess potent cytotoxic mechanisms that need to be tightly controlled. Here, we explored the regulation and function of GPR56/ADGRG1, an adhesion G protein-coupled receptor implicated in developmental processes and expressed distinctively in mature NK cells. Expression of GPR56 was triggered by Hobit (a homolog of Blimp-1 in T cells) and declined upon cell activation. Through studying NK cells from polymicrogyria patients with disease-causing mutations in ADGRG1, encoding GPR56, and NK-92 cells ectopically expressing the receptor, we found that GPR56 negatively regulates immediate effector functions, including production of inflammatory cytokines and cytolytic proteins, degranulation, and target cell killing. GPR56 pursues this activity by associating with the tetraspanin CD81. We conclude that GPR56 inhibits natural cytotoxicity of human NK cells.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 333 Tao-Yuan, Taiwan.
authors.forename: Gin-Wen
authors.initials: GW
authors.lastname: Chang
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Cheng-Chih
authors.initials: CC
authors.lastname: Hsiao
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 333 Tao-Yuan, Taiwan.
authors.forename: Yen-Ming
authors.initials: YM
authors.lastname: Peng
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Vieira Braga
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.
authors.forename: Natasja A M
authors.initials: NA
authors.lastname: Kragten
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; Renal Transplant Unit, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Ester B M
authors.initials: EB
authors.lastname: Remmerswaal
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Martijn D B
authors.initials: MD
authors.lastname: van de Garde
authors.affiliation: Department of Child Neurology, Neurogenetics Clinic, Schneider Children's Medical Center, Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Straussberg
authors.affiliation: Institute for Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany.
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: König
authors.affiliation: Institute for Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany.
authors.forename: Evi
authors.initials: E
authors.lastname: Kostenis
authors.affiliation: Dental School, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Vera
authors.initials: V
authors.lastname: Knäuper
authors.affiliation: Department of Immunology, University Medical Center Utrecht, 3584 EA Utrecht, the Netherlands.
authors.forename: Linde
authors.initials: L
authors.lastname: Meyaard
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.
authors.forename: Klaas P J M
authors.initials: KP
authors.lastname: van Gisbergen
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 333 Tao-Yuan, Taiwan; Chang Gung Immunology Consortium and Department of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, 333 Tao-Yuan, Taiwan. Electronic address: hhlin@mail.cgu.edu.tw.
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands. Electronic address: j.hamann@amc.uva.nl.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D054992:Immunological Synapses / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054220:Malformations of Cortical Development / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000378:metabolism*; D060225:Tetraspanin 28 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C118925:ADGRG1 protein, human; D016207:Cytokines; D018836:Inflammation Mediators; D043562:Receptors, G-Protein-Coupled; D060225:Tetraspanin 28; D014157:Transcription Factors
keywords: NK cells; adhesion GPCRs; cytotoxicity; immune regulation; transcription factor