Specific expression of GPR56 by human cytotoxic lymphocytes

Abstract

We here report the existence of a new cluster of adhesion-GPCRs in human immune cells. Analysis of a comprehensive immune cell transcriptome dataset indicated that expression of the closely related receptors, GPR56, GPR97, and GPR114, is associated with single lymphocyte and granulocyte subsets. Applying flow cytometric analysis with newly generated mAb, we show that expression of GPR56 is restricted to cytotoxic NK and T lymphocytes, including CD8(+), CD4(+), and γδ T cells. Primary infection with human CMV, which generates a vast population of CD8(+) T cells with an effector phenotype, induced a strong increase in GPR56 expression in virus-specific CD8(+) T cells that remained detectable during latency. In NK-92 cells, ectopic expression of GPR56 inhibited spontaneous and SDF-1-stimulated cell migration. Our data suggest that GPR56 expression is a common trait of human cytotoxic lymphocytes and might affect the migratory properties of these cells.

Shear Stress–Dependent Downregulation of the Adhesion-G Protein–Coupled Receptor CD97 on Circulating Leukocytes upon Contact with Its Ligand CD55

“…Besides CD55, CD97 binds the glycosaminoglycan dermatan sulfate, the integrin a5b1, and Thy-1/CD90 through different sites within the extracellular subunit (12,13,20). Similar characteristics have been reported for GPR56, an aGPCR expressed by neurons, various malignant cells, and cytotoxic lymphocytes (2,44). GPR56 binds different ligands in man and mouse, including tissue transglutaminase 2 and collagen III (14,19,45).…”

The integrin–collagen connection – a glue for tissue repair?

“…GPR56 is present on meningeal fibroblasts, oligodendrocytes, melanoma cells and cytotoxic NK and T lymphocytes (Chiang et al, 2011;Peng et al, 2011;Yang and Xu, 2012). Human GPR56 mutations cause a brain malformation called bilateral frontoparietal polymicrogyria (Chiang et al, 2011).…”

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

“…Many more Adhesion GPCRs are widely distributed, such as the above-discussed ADGRE5 (CD97) and the ADGRLs, ADGRCs, and ADGRBs (latrophilins, CELSRs, and BAIs). Likewise, ADGRG1 (GPR56), originally identified in melanoma cells, is also expressed by various progenitor cells and by cytotoxic lymphocytes (Zendman et al, 1999;Piao et al, 2004;Della Chiesa et al, 2010;Peng et al, 2011). Of note, extracellular interaction partners (see section V) have been ascribed mostly to Adhesion GPCRs that have a rather wide cellular distribution.…”

“…The presence of ADGRG1 (GPR56), ADGRG3 (GPR97), and ADGRG5 (GPR114) in leukocyte subsets (Della Chiesa et al, 2010;Peng et al, 2011) implies that these Adhesion GPCRs have immune-related functions that need to be explored. These receptors may also mediate hematopoietic stem cell repopulation and retention of myeloid cells within the bone marrow niche (Saito et al, 2013).…”