The G Protein-Coupled Receptor GPR56 Is an Inhibitory Checkpoint for NK Cell Migration.

Autor:	Palacios D; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Majhi RK; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Center of Excellence in Cancer, Gangwal School of Medical Sciences and Technology, Mehta Family Center for Engineering in Medicine, Department of Biological Sciences and Bioengineering, IIT Kanpur, India., Szabo EK; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Clement D; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Lachota M; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Laboratory of Cellular and Genetic Therapies, Medical University of Warsaw, Warsaw, Poland., Netskar H; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Penna L; Finnish Red Cross Blood Service, Research and Development, Helsinki, Finland., Krokeide SZ; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Vincenti M; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Kveberg L; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Malmberg KJ; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway.; Centre for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Sweden.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Nov 01; Vol. 213 (9), pp. 1349-1357.
DOI:	10.4049/jimmunol.2400228
Abstrakt:	G protein-coupled receptors (GPCRs) represent the largest family of surface receptors and are responsible for key physiological functions, including cell growth, neurotransmission, hormone release, and cell migration. The GPCR 56 (GPR56), encoded by ADGRG1, is an adhesion GPCR found on diverse cell types, including neural progenitor cells, melanoma cells, and lymphocytes, such as effector memory T cells, γδ T cells, and NK cells. Using RNA-sequencing and high-resolution flow cytometry, we found that GPR56 mRNA and protein expression increased with NK cell differentiation, reaching its peak in adaptive NK cells. Small interfering RNA silencing of GPR56 led to increased spontaneous and chemokine-induced migration, suggesting that GPR56 functions as an upstream checkpoint for migration of highly differentiated NK cells. Increased NK cell migration could also be induced by agonistic stimulation of GPR56 leading to rapid internalization and deactivation of the receptor. Mechanistically, GPR56 ligation and downregulation were associated with transcriptional coactivator with PDZ-binding motif translocation to the nucleus and increased actin polymerization. Together, these data provide insights into the role of GPR56 in the migratory behavior of human NK cell subsets and may open possibilities to improve NK cell infiltration into cancer tissues by releasing a migratory checkpoint. (Copyright © 2024 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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