The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells
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...
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doaj-5fb9b1597dee429ea865037cd9e6f62f2020-11-24T22:01:13ZengElsevierCell Reports2211-12472016-05-011581757177010.1016/j.celrep.2016.04.053The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK CellsGin-Wen Chang0Cheng-Chih Hsiao1Yen-Ming Peng2Felipe A. Vieira Braga3Natasja A.M. Kragten4Ester B.M. Remmerswaal5Martijn D.B. van de Garde6Rachel Straussberg7Gabriele M. König8Evi Kostenis9Vera Knäuper10Linde Meyaard11René A.W. van Lier12Klaas P.J.M. van Gisbergen13Hsi-Hsien Lin14Jörg Hamann15Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 333 Tao-Yuan, TaiwanDepartment of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the NetherlandsGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 333 Tao-Yuan, TaiwanDepartment of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the NetherlandsDepartment of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the NetherlandsDepartment of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the NetherlandsDepartment of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the NetherlandsDepartment of Child Neurology, Neurogenetics Clinic, Schneider Children’s Medical Center, Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelInstitute for Pharmaceutical Biology, University of Bonn, 53115 Bonn, GermanyInstitute for Pharmaceutical Biology, University of Bonn, 53115 Bonn, GermanyDental School, Cardiff University, Cardiff CF14 4XN, UKDepartment of Immunology, University Medical Center Utrecht, 3584 EA Utrecht, the NetherlandsDepartment of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the NetherlandsDepartment of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the NetherlandsGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 333 Tao-Yuan, TaiwanDepartment of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the NetherlandsNatural 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.http://www.sciencedirect.com/science/article/pii/S2211124716304806adhesion GPCRscytotoxicityimmune regulationNK cellstranscription factor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells Cell Reports adhesion GPCRs cytotoxicity immune regulation NK cells transcription factor |
author_facet |
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 |
author_sort |
Gin-Wen Chang |
title |
The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells |
title_short |
The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells |
title_full |
The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells |
title_fullStr |
The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells |
title_full_unstemmed |
The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells |
title_sort |
adhesion g protein-coupled receptor gpr56/adgrg1 is an inhibitory receptor on human nk cells |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-05-01 |
description |
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. |
topic |
adhesion GPCRs cytotoxicity immune regulation NK cells transcription factor |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716304806 |
work_keys_str_mv |
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