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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2016-05-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124716304806
id doaj-5fb9b1597dee429ea865037cd9e6f62f
record_format Article
spelling 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 AT ginwenchang theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT chengchihhsiao theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT yenmingpeng theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT felipeavieirabraga theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT natasjaamkragten theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT esterbmremmerswaal theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT martijndbvandegarde theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT rachelstraussberg theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT gabrielemkonig theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT evikostenis theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT veraknauper theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT lindemeyaard theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT reneawvanlier theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT klaaspjmvangisbergen theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT hsihsienlin theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT jorghamann theadhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT ginwenchang adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT chengchihhsiao adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT yenmingpeng adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT felipeavieirabraga adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT natasjaamkragten adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT esterbmremmerswaal adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT martijndbvandegarde adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT rachelstraussberg adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT gabrielemkonig adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT evikostenis adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT veraknauper adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT lindemeyaard adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT reneawvanlier adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT klaaspjmvangisbergen adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT hsihsienlin adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
AT jorghamann adhesiongproteincoupledreceptorgpr56adgrg1isaninhibitoryreceptoronhumannkcells
_version_ 1725841018395295744