title: GPR56 as a novel marker identifying the CD56dull CD16+ NK cell subset both in blood stream and in inflamed peripheral tissues.
abstract: To define novel human NK cell markers, we generated two mAbs specific for G-protein-coupled receptor 56 (GPR56), a surface glycoprotein that appears to be involved in cell-to-cell and cell-to-matrix interactions. GPR56 has been described in selected normal tissues, and in certain tumors, while, as yet, its expression on leukocytes is unknown. In this study, we show that anti-GPR56 mAbs, among leukocytes, prevalently recognize NK cells. In particular, these mAbs brightly stain CD56(dull) CD16(+) NK cells while react poorly with CD56(bright) CD16(+/-) NK cells. Consistently, we found that GPR56 was expressed on NK cells populating inflamed peripheral tissues while it was absent in lymph node-derived NK cells. We also show that activating stimuli, such as cytokines or exposure to monocyte-derived dendritic cell, down-regulate NK cell expression of GPR56 both at the protein and at the transcriptional level. Interestingly, IL-18, known to induce de novo expression of CCR7 on CD56(dull) CD16(+) NK cells, displayed the highest capability of modulating GPR56. Thus, together with the identification of GPR56 as a novel marker capable of discriminating different NK cells subsets, our data suggest that GPR56 may take part to the mechanisms regulating NK cell migration through the blood stream, peripheral tissues and lymph nodes.
authors.affiliation: Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16132 Genova, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Della Chiesa
authors.forename: Michela
authors.initials: M
authors.lastname: Falco
authors.forename: Silvia
authors.initials: S
authors.lastname: Parolini
authors.forename: Francesca
authors.initials: F
authors.lastname: Bellora
authors.forename: Andrea
authors.initials: A
authors.lastname: Petretto
authors.forename: Elisa
authors.initials: E
authors.lastname: Romeo
authors.forename: Mirna
authors.initials: M
authors.lastname: Balsamo
authors.forename: Marco
authors.initials: M
authors.lastname: Gambarotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Scordamaglia
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tabellini
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Cristina
authors.initials: C
authors.lastname: Bottino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Massimo
authors.initials: M
authors.lastname: Vitale
mesh_terms: D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000378:metabolism; D019002:CD56 Antigen / Q000032:analysis*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D058851:GPI-Linked Proteins; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000032:analysis*; D014162:Transfection
chemical_list: C118925:ADGRG1 protein, human; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007378:Interleukins; D043562:Receptors, G-Protein-Coupled; D017452:Receptors, IgG