IgE依存的・非依存的なマスト細胞の活性化とアレルギー応答の制御機序

抄録

Mast cells play a central role in IgE-dependent allergic responses. Engagement of antigen-specific IgE-bound FceRI with the same antigen induces mast cell degranulation, leading to the immediate hypersensitivity reaction. On the other hand, stimulation with cationic drugs (e.g., compound 48/80) induces IgE-independent degranulation of connective tissue mast cells via Mrgprb2, the murine homolog of MRGPRX2, leading to pseudo-allergic reaction. However, an inhibitory receptor CD300f down-regulates the excessive activation of mast cells in vivo. In fact, both FceRI-mediated anaphylactic responses and Mrgprb2-mediated pseudo-allergic responses are enhanced in CD300f-deficient mice compared to wild-type mice. We have previously identified ceramide as a ligand for CD300f. Consistently, administration of ceramide liposomes, prepared by using an extruder, inhibits both anaphylactic and pseudo-allergic responses in mice. In addition, we recently developed a new method to generate stable ceramide liposomes and demonstrated that intranasal administration of newly-generated ceramide liposomes inhibits ragweed pollen-induced allergic rhinitis in murine models. Thus, intranasal administration of ceramide liposomes will be a useful therapeutic strategy against allergic rhinitis.