Kim Hwan Soo, Kawakami Yu, Kasakura Kazumi, Kawakami Toshiaki
Division of Cell Biology, La Jolla Institute for Immunology, La Jolla, California, 92037, USA.
Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
F1000Res. 2020 Mar 19;9. doi: 10.12688/f1000research.22037.1. eCollection 2020.
Mast cells are innate immune cells that intersect with the adaptive immunity and play a crucial role in the initiation of allergic reactions and the host defense against certain parasites and venoms. When activated in an allergen- and immunoglobulin E (IgE)-dependent manner, these cells secrete a large variety of allergenic mediators that are pre-stored in secretory granules or -synthesized. Traditionally, studies have predominantly focused on understanding this mechanism of mast cell activation and regulation. Along this line of study, recent studies have shed light on what structural features are required for allergens and how IgE, particularly anaphylactic IgE, is produced. However, the last few years have seen a flurry of new studies on IgE-independent mast cell activation, particularly via Mrgprb2 (mouse) and MRGPRX2 (human). These studies have greatly advanced our understanding of how mast cells exert non-histaminergic itch, pain, and drug-induced pseudoallergy by interacting with sensory neurons. Recent studies have also characterized mast cell activation and regulation by interleukin-33 (IL-33) and other cytokines and by non-coding RNAs. These newly identified mechanisms for mast cell activation and regulation will further stimulate the allergy/immunology community to develop novel therapeutic strategies for treatment of allergic and non-allergic diseases.
肥大细胞是先天性免疫细胞，与适应性免疫相互作用，在过敏反应的启动以及宿主抵御某些寄生虫和毒液的过程中发挥关键作用。当以过敏原和免疫球蛋白E（IgE）依赖的方式被激活时，这些细胞会分泌大量预先储存在分泌颗粒中或合成的过敏介质。传统上，研究主要集中在理解肥大细胞激活和调节的机制。沿着这条研究路线，最近的研究揭示了过敏原需要哪些结构特征以及IgE，特别是过敏性IgE是如何产生的。然而，在过去几年里，出现了一系列关于IgE非依赖性肥大细胞激活的新研究，特别是通过Mrgprb2（小鼠）和MRGPRX2（人类）。这些研究极大地推进了我们对肥大细胞如何通过与感觉神经元相互作用产生非组胺能瘙痒、疼痛和药物诱导的假过敏的理解。最近的研究还描述了白细胞介素-33（IL-33）和其他细胞因子以及非编码RNA对肥大细胞的激活和调节。这些新发现的肥大细胞激活和调节机制将进一步刺激过敏/免疫学界开发治疗过敏性和非过敏性疾病的新治疗策略。
