The leukocyte receptor CD84 inhibits FcɛRI-mediated signaling through homophilic interaction in transfected RBL-2H3 cells

Signaling through the high-affinity receptor for immunoglobulin E (FcɛRI) 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 FcɛRI-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 ΔY324) reversed this inhibitory profile. These data suggest that CD84 may play a role in modulating FcɛRI-mediated signaling in mast cells. Thus, CD84 could play a protective role against undesired allergic and inflammatory responses.