The adhesion G protein-coupled receptor GPR56/ADGRG1 in cytotoxic lymphocytes

GPR56/ADGRG1 is an adhesion G protein-coupled receptor connected to brain development, haematopoiesis, male fertility, and tumorigenesis. Nevertheless, expression of GPR56 is not restricted to developmental processes. Studies over the last years have demonstrated a marked presence of GPR56 in human cytotoxic NK and T cells. Expression of GPR56 in these cells is driven by the transcription factor HOBIT, corresponds with the production of cytolytic mediators and the presence of CX(3)CR1 and CD57, indicates a state of terminal differentiation and cellular exhaustion, and disappears upon cellular activation. Functional studies indicate that GPR56 regulates cell migration and effector functions and thereby acts as an inhibitory immune checkpoint. We here discuss the current state of knowledge regarding GPR56 in cytotoxic lymphocytes.

Automated summary

GPR56/ADGRG1 is an adhesion G protein-coupled receptor with significant roles in brain development, haematopoiesis, male fertility, and tumorigenesis. Recent studies have shown that GPR56 is also present in human cytotoxic NK and T cells, where its expression is driven by the transcription factor HOBIT and associated with cytolytic mediators, CX(3)CR1 and CD57. It indicates a state of terminal differentiation and cellular exhaustion, and disappears upon cellular activation. Functional studies reveal that GPR56 regulates cell migration and effector functions, acting as an inhibitory immune checkpoint. This article discusses the current understanding of GPR56 in cytotoxic lymphocytes.