Role of GPR56 as a Differentiation Marker and Inhibitory Adhesion G Protein-Coupled Receptor in Human NK Cell

protein-coupled receptor 56 (GPR56), a member of the adhesion-class G protein-coupled receptor (adhesion-GPCR) family, has been implicated in many physiopathological processes such as brain cortical formation, hematopoietic stem cell maintenance, male gonad development, myoblast fusion, muscle hypertrophy, and tumorigenesis. In the human immune system, GPR56 is distinctively expressed in cytotoxic lymphocytes including CD56dim natural killer (NK) cells and CD27–CD45RA+ T cells. NK cells are the innate lymphoid cells important for the elimination of virus-infected cells and transformed cells. Our recent preliminary results indicate that GPR56 is restrictedly expressed in terminally differentiated mature but not proliferating immature human NK cell and plays an inhibitory role in NK cell function. We here aim to further explore the regulation and function of GPR56 in NK cell. Specifically, we propose to examine the regulation of GPR56 expression during NK cell differentiation and maturation. Next, the role of GPR56 and the molecular mechanisms mediated by GPR56 in modulating NK cell effector functions, including production of inflammatory cytokines and cytolytic enzymes, degranulation, and target cell killing will be thoroughly investigated. Finally, the dynamic molecular changes of GPR56 protein during NK cell activation will be pursued. We hope to delineate the regulatory mechanism and functional role of GPR56 in human NK cell. Results of this study are expected to provide critical insights into how the differentiation and/or function of NK cell are regulated by GPR56 receptor signaling.

Project ID:PC10501-2036
External Project ID:MOST104-2320-B182-035-MY3