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

被引:82
作者
Chang, Gin-Wen [1 ]
Hsiao, Cheng-Chih [2 ]
Peng, Yen-Ming [1 ]
Braga, Felipe A. Vieira [3 ]
Kragten, Natasja A. M. [3 ]
Remmerswaal, Ester B. M. [2 ,4 ]
van de Garde, Martijn D. B. [2 ]
Straussberg, Rachel [5 ,6 ]
Koenig, Gabriele M. [7 ]
Kostenis, Evi [7 ]
Knauper, Vera [8 ]
Meyaard, Linde [9 ]
van Lier, Rene A. W. [3 ]
van Gisbergen, Klaas P. J. M. [3 ]
Lin, Hsi-Hsien [1 ,10 ,11 ]
Hamann, Jorg [2 ]
机构
[1] Chang Gung Univ, Coll Med, Grad Inst Biomed Sci, Tao Yuan 333, Taiwan
[2] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Dept Hematopoiesis, Sanquin Res & Landsteiner Lab, NL-1066 CX Amsterdam, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, Renal Transplant Unit, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
[5] Schneider Childrens Med Ctr, Dept Child Neurol, Neurogenet Clin, Petah Tiqwa, Israel
[6] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
[7] Univ Bonn, Inst Pharmaceut Biol, D-53115 Bonn, Germany
[8] Cardiff Univ, Sch Dent, Cardiff CF14 4XN, S Glam, Wales
[9] Univ Med Ctr Utrecht, Dept Immunol, NL-3584 EA Utrecht, Netherlands
[10] Chang Gung Mem Hosp Linkou, Chang Gung Immunol Consortium, Tao Yuan 333, Taiwan
[11] Chang Gung Mem Hosp Linkou, Dept Anat Pathol, Tao Yuan 333, Taiwan
来源
CELL REPORTS | 2016年 / 15卷 / 08期
关键词
NATURAL-KILLER-CELLS; VIRUS ENVELOPE PROTEIN; OLIGODENDROCYTE DEVELOPMENT; SURFACE EXPRESSION; TETHERED AGONIST; GPR56; PROTEIN; BONE-MARROW; T-BET; EOMES; DIFFERENTIATION;
D O I
10.1016/j.celrep.2016.04.053
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1757 / 1770
页数:14
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