The leukocyte receptor CD84 inhibits Fc epsilon RI-mediated signaling through homophilic interaction in transfected RBL-2H3 cells.
Signaling through the high-affinity receptor for immunoglobulin E (Fc epsilon RI) results in the coordinated activation of tyrosine kinases, thus leading to calcium mobilization, degranulation, and leukotriene and cytokine synthesis. Here, we show that CD84, a member of the CD150 family of leukocyte receptors, inhibits Fc epsilon RI-mediated mast cell degranulation in CD84-transfected rat basophilic leukaemia-2H3 mast cell line cells (RBL-2H3) through homophilic interaction. There was no reduction in overall protein phosphorylation following IgE triggering in CD84 RBL-2H3 cells. Indeed, phosphorylation of Dok-1 and c-Cbl increased in CD84 RBL-2H3, suggesting that inhibition is mediated by these molecules. MAP kinase phosphorylation (ERK1/2, JNK and p38) and cytokine synthesis were impaired in CD84 RBL-2H3. This inhibitory mechanism was independent of SAP and SHP-2 recruitment. Interestingly, CD84 mutants in tyrosines (Y279F and DeltaY324) reversed this inhibitory profile. These data suggest that CD84 may play a role in modulating Fc epsilon RI-mediated signaling in mast cells. Thus, CD84 could play a protective role against undesired allergic and inflammatory responses.
Oliver-Vila
Irene
I
Grup Immunoreceptors, Institut d'Investigació August Pi i Sunyer, Department de Biologia Cellular i Anatomia Patològica, Facultat Medicina, Universitat de Barcelona, Barcelona, Spain.
Saborit-Villarroya
Ifigènia
I
Engel
Pablo
P
Martin
Margarita
M
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology*; D019556:COS Cells; D015550:Cell Degranulation / Q000276:immunology; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000276:immunology; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D017455:Receptors, IgE / Q000037:antagonists & inhibitors* / Q000276:immunology*; D015398:Signal Transduction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; C498970:CD84 protein, human; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D017455:Receptors, IgE; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D007073:Immunoglobulin E; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases