Combined effect of Dex and CD300a, activated by an anti-CD300a agonistic mAbs, on human and murine MCs functions and in anti-IgE-induced peritonitis in mouse model was evaluated.First, we investigated whether Dex (1-1000 nM) would influence the expression of CD300a on human CBMCs and murine BMMCs.Flow cytometry (FC) anal. revealed that following 18 h of incubation with Dex, CD300a expression in both cell types remained unchanged.IL-10 release was significantly increased in mouse MCs with the combined treatment compared with the relevant mono-treatments indicating the cooperation of Dex and anti-CD300a in activation of inhibitory cellular pathways.FC anal. in BMMCs showed only a minor reduction in phosphorylation levels of all three signalling mols. following combined treatment with Dex and anti-CD300a in comparison to their mono-treatments.A significant additive decrease (by ∼90%) in both these pre-stored MCs mediators was detected in mice treated with Dex and anti-CD300a agonistic mAbs compared to their resp. mono-treatments.In summary, the present study demonstrates a co-inhibitory effect for Dex and anti-CD300a mAbs on degranulation and cytokine release from BMMCs and on cytokine release from CBMCs.In vivo data show a similar co-inhibitory effect.The combined use of GCs and mAbs against CD300a and perhaps other inhibitory receptors expressed by inflammatory cells might become a novel approach to decrease GCs doses given in allergic and other inflammatory diseases.