The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells
Gin-Wen Chang,
Cheng-Chih Hsiao,
Yen-Ming Peng,
Felipe A. Vieira Braga,
Natasja A.M. Kragten,
Ester B.M. Remmerswaal,
Martijn D.B. van de Garde,
Rachel Straussberg,
Gabriele M. König,
Evi Kostenis,
Vera Knäuper,
Linde Meyaard,
René A.W. van Lier,
Klaas P.J.M. van Gisbergen,
Hsi-Hsien Lin,
Jörg Hamann
Affiliations
Gin-Wen Chang
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 333 Tao-Yuan, Taiwan
Cheng-Chih Hsiao
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Yen-Ming Peng
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 333 Tao-Yuan, Taiwan
Felipe A. Vieira Braga
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands
Natasja A.M. Kragten
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands
Ester B.M. Remmerswaal
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Martijn D.B. van de Garde
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Rachel Straussberg
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
Gabriele M. König
Institute for Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany
Evi Kostenis
Institute for Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany
Vera Knäuper
Dental School, Cardiff University, Cardiff CF14 4XN, UK
Linde Meyaard
Department of Immunology, University Medical Center Utrecht, 3584 EA Utrecht, the Netherlands
René A.W. van Lier
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands
Klaas P.J.M. van Gisbergen
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands
Hsi-Hsien Lin
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 333 Tao-Yuan, Taiwan
Jörg Hamann
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
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.
