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The adhesion G protein-coupled receptor GPR56/ADGRG1 is an inhibitory receptor on human NK cells

Hsiao, Cheng-Chih, Chang, Gin-Wen, Peng, Yen-Ming, Braga, Felipe A. Vieira, Kragten, Natasja A.M., Remmerswaal, Ester B. M., Garde, Martijn D. B. van de, Straussberg, Rachel, König, Gabriele M., Kostenis, Evi, Knauper, Vera, Meyaard, Linde, van Lier, René A.W., van Gisbergen, Klaas P.J.M., Lin, Hsi-Hsien and Hamann, Jörg 2016. The adhesion G protein-coupled receptor GPR56/ADGRG1 is an inhibitory receptor on human NK cells. Cell Reports 15 (8) , pp. 1757-1770. 10.1016/j.celrep.2016.04.053

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Abstract

Natural killer (NK) cells possess potent cytotoxic mechanisms that need to be tightly controlled. We here 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, and declined upon cell activation. Through studying NK cells from polymicrogyria patients with disease-causing mutations in the ADGRG1 gene, 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/2211-1247/ (accessed 21/04/2016)
Publisher: Cell Press
ISSN: 2211-1247
Funders: Tenovus
Date of First Compliant Deposit: 20 April 2016
Date of Acceptance: 14 April 2016
Last Modified: 27 Jun 2019 08:41
URI: http://orca.cf.ac.uk/id/eprint/89460

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