GPR56 as a novel marker identifying the CD56dull CD16+ NK cell subset both in blood stream and in inflamed peripheral tissues.
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.
Della Chiesa
Mariella
M
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16132 Genova, Italy.
Falco
Michela
M
Parolini
Silvia
S
Bellora
Francesca
F
Petretto
Andrea
A
Romeo
Elisa
E
Balsamo
Mirna
M
Gambarotti
Marco
M
Scordamaglia
Francesca
F
Tabellini
Giovanna
G
Facchetti
Fabio
F
Vermi
William
W
Bottino
Cristina
C
Moretta
Alessandro
A
Vitale
Massimo
M
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
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