School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
Cells. 2021 Apr 27;10(5):1033. doi: 10.3390/cells10051033.
Mas-related G-protein coupled receptor member X2 (MRGPRX2) is a class A GPCR expressed on mast cells. Mast cells are granulated tissue-resident cells known for host cell response, allergic response, and vascular homeostasis. Immunoglobulin E receptor (FcεRI)-mediated mast cell activation is a well-studied and recognized mechanism of allergy and hypersensitivity reactions. However, non-IgE-mediated mast cell activation is less explored and is not well recognized. After decades of uncertainty, MRGPRX2 was discovered as the receptor responsible for non-IgE-mediated mast cells activation. The puzzle of non-IgE-mediated pseudo-allergic reaction is unlocked by MRGPRX2, evidenced by a plethora of reported endogenous and exogenous MRGPRX2 agonists. MRGPRX2 is exclusively expressed on mast cells and exhibits varying affinity for many molecules such as antimicrobial host defense peptides, neuropeptides, and even US Food and Drug Administration-approved drugs. The discovery of MRGPRX2 has changed our understanding of mast cell biology and filled the missing link of the underlying mechanism of drug-induced MC degranulation and pseudo-allergic reactions. These non-canonical characteristics render MRGPRX2 an intriguing player in allergic diseases. In the present article, we reviewed the emerging role of MRGPRX2 as a non-IgE-mediated mechanism of mast cell activation in pseudo-allergic reactions. We have presented an overview of mast cells, their receptors, structural insight into MRGPRX2, MRGPRX2 agonists and antagonists, the crucial role of MRGPRX2 in pseudo-allergic reactions, current challenges, and the future research direction.
Mas 相关 G 蛋白偶联受体成员 X2（MRGPRX2）是一种 A 类 G 蛋白偶联受体，表达于肥大细胞上。肥大细胞是一种颗粒状组织驻留细胞，以宿主细胞反应、过敏反应和血管稳态为特征。免疫球蛋白 E 受体（FcεRI）介导的肥大细胞活化是过敏和超敏反应的一种研究充分且公认的机制。然而，非 IgE 介导的肥大细胞活化研究较少，也未得到充分认识。经过几十年的不确定，MRGPRX2 被发现是负责非 IgE 介导的肥大细胞活化的受体。MRGPRX2 解开了非 IgE 介导的假性过敏反应的谜题，大量报道的内源性和外源性 MRGPRX2 激动剂证明了这一点。MRGPRX2 仅表达于肥大细胞上，对许多分子具有不同的亲和力，如抗菌宿主防御肽、神经肽，甚至美国食品和药物管理局批准的药物。MRGPRX2 的发现改变了我们对肥大细胞生物学的理解，并填补了药物诱导的肥大细胞脱颗粒和假性过敏反应潜在机制的缺失环节。这些非典型特征使 MRGPRX2 成为过敏疾病中一个有趣的参与者。在本文中，我们综述了 MRGPRX2 作为非 IgE 介导的肥大细胞活化机制在假性过敏反应中的新作用。我们概述了肥大细胞、它们的受体、MRGPRX2 的结构见解、MRGPRX2 激动剂和拮抗剂、MRGPRX2 在假性过敏反应中的关键作用、当前的挑战以及未来的研究方向。
