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

doi:10.1016/j.celrep.2016.04.053

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

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

81 Scopus citations

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.

Original language	English
Pages (from-to)	1757-1770
Number of pages	14
Journal	Cell Reports
Volume	15
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2016.04.053
State	Published - 24 May 2016

Funding

Funders	Funder number
Thyssen Foundation	2015-00387, FOR 2149
Ministry of Education
Chang Gung Memorial Hospital	CMRPD1D0391-2, CMRPD1A0181-3, CMRPD1D0072-3
Deutsche Forschungsgemeinschaft	FOR 2372
Ministry of Science and Technology, Taiwan	MOST101-2320-B-182-029-MY3, MOST104-2320-B-182-035-MY3
European Federation of Immunological Societies

Keywords

Adhesion GPCRs
Cytotoxicity
Immune regulation
NK cells
Transcription factor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2016.04.053

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Chang, G. W., Hsiao, C. C., Peng, Y. M., Vieira Braga, F. A., Kragten, N. A. M., Remmerswaal, E. B. M., van de Garde, M. D. B., Straussberg, R., König, G. M., Kostenis, E., Knäuper, V., Meyaard, L., van Lier, R. A. W., van Gisbergen, K. P. J. M., Lin, H. H., & Hamann, J. (2016). The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells. Cell Reports, 15(8), 1757-1770. https://doi.org/10.1016/j.celrep.2016.04.053

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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.",

keywords = "Adhesion GPCRs, Cytotoxicity, Immune regulation, NK cells, Transcription factor",

author = "Chang, {Gin Wen} and Hsiao, {Cheng Chih} and Peng, {Yen Ming} and {Vieira Braga}, {Felipe A.} and Kragten, {Natasja A.M.} and Remmerswaal, {Ester B.M.} and {van de Garde}, {Martijn D.B.} and Rachel Straussberg and K{\"o}nig, {Gabriele M.} and Evi Kostenis and Vera Kn{\"a}uper and Linde Meyaard and {van Lier}, {Ren{\'e} A.W.} and {van Gisbergen}, {Klaas P.J.M.} and Lin, {Hsi Hsien} and J{\"o}rg Hamann",

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year = "2016",

month = may,

day = "24",

doi = "10.1016/j.celrep.2016.04.053",

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Chang, GW, Hsiao, CC, Peng, YM, Vieira Braga, FA, Kragten, NAM, Remmerswaal, EBM, van de Garde, MDB, Straussberg, R, König, GM, Kostenis, E, Knäuper, V, Meyaard, L, van Lier, RAW, van Gisbergen, KPJM, Lin, HH & Hamann, J 2016, 'The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells', Cell Reports, vol. 15, no. 8, pp. 1757-1770. https://doi.org/10.1016/j.celrep.2016.04.053

TY - JOUR

T1 - The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells

AU - Chang, Gin Wen

AU - Hsiao, Cheng Chih

AU - Peng, Yen Ming

AU - Vieira Braga, Felipe A.

AU - Kragten, Natasja A.M.

AU - Remmerswaal, Ester B.M.

AU - van de Garde, Martijn D.B.

AU - Straussberg, Rachel

AU - König, Gabriele M.

AU - Kostenis, Evi

AU - Knäuper, Vera

AU - Meyaard, Linde

AU - van Lier, René A.W.

AU - van Gisbergen, Klaas P.J.M.

AU - Lin, Hsi Hsien

AU - Hamann, Jörg

PY - 2016/5/24

Y1 - 2016/5/24

N2 - 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.

AB - 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.

KW - Adhesion GPCRs

KW - Cytotoxicity

KW - Immune regulation

KW - NK cells

KW - Transcription factor

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C2 - 27184850

AN - SCOPUS:84966692466

SN - 2211-1247

VL - 15

SP - 1757

EP - 1770

JO - Cell Reports

JF - Cell Reports

IS - 8

ER -

The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells

Abstract

Funding

Keywords

UN SDGs

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