MRGPRX2介导肥大细胞脱颗粒在特应性皮炎非组胺依赖性瘙痒中的作用

The Role of MRGPRX2-Mediated Mast Cell Degranulation in Nonhistamine-Dependent Pruritus in Atopic Dermatitis

特应性皮炎(atopic dermatitis,AD)相关的慢性瘙痒是一种典型的非组胺依赖性瘙痒,由于抗组胺药物通常不能对其进行有效控制,因而非组胺依赖性瘙痒及其缓解机制日益受到关注。肥大细胞(mast cells,MCs)除了可以通过IgE与FcεRⅠ受体结合引发经典组胺依赖性瘙痒外,也可通过Mas相关的G蛋白偶联受体X2(Mas-related G protein-coupled receptors X2,MRGPRX2)引发非组胺依赖性瘙痒并参与特应性皮炎的进程。MRGPRX2所介导的MCs快速脱颗粒通过激活蛋白酶激活受体-2(protease-activated receptor-2,PAR-2),引起非组胺依赖性瘙痒,MCs-神经元单位改变趋于一种不稳定的平衡状态,形成神经源性炎症反应。缺失或抑制MRGPRX2可以显著降低MCs脱颗粒,预防并治疗急性和慢性过敏反应。因此,MRGPRX2介导的MCs脱颗粒在特应性皮炎非组胺依赖慢性瘙痒中起到重要作用,通过抑制MRGPRX2减少MCs脱颗粒已经成为改善特应性皮炎的新靶点。

The chronic pruritus related to atopic dermatitis(AD)is a typical nonhistamine-dependent pruritus,which can not be effectively controlled by antihistamines.Therefore,nonhistamine-dependent pruritus and its relief mechanisms have received increasing attention in recent years.Mast cells(MCs)not only induce classical nonhistamine-dependent pruritus through IgE binding to FcεRⅠreceptors,in addition to major contribution of classical FcεRI/IgE-activated mast cells(MCs),but also participate in the progression of AD for nonhistamine-dependent pruritus induced by Mas-related G protein-coupled receptors X2(MRGPRX2).The rapid degranulation of MCs mediated by MRGPRX2 activates protease-activated receptor-2(PAR-2),leading to nonhistamine-dependent pruritus.The changes in the MCs-neuronal unit tend towards an unstable equilibrium,resulting in neurogenic inflammation.Deletion or inhibition of MRGPRX2 can significantly reduce MCs degranulation,and prevent or treat acute and chronic allergic reactions.Therefore,MRGPRX2-mediated MCs degranulation plays an important role in AD-related chronic nonhistamine-dependent pruritus,and reducing MCs degranulation by inhibiting MRGPRX2 has become a new target for improving AD.