The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells
2016
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.
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