Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Pharmacol Ther. 2021 Apr;220:107718. doi: 10.1016/j.pharmthera.2020.107718. Epub 2020 Oct 29.
Mast cells are tissue-resident immune cells that play key roles in the initiation and perpetuation of allergic inflammation, usually through IgE-mediated mechanisms. Mast cells are, however, evolutionary ancient immune cells that can be traced back to urochordates and before the emergence of IgE antibodies, suggesting their involvement in antibody-independent biological functions, many of which are still being characterized. Herein, we summarize recent advances in understanding the roles of mast cells in health and disease, partly through the study of emerging non-IgE receptors such as the Mas-related G protein-coupled receptor X2, implicated in pseudo-allergic reactions as well as in innate defense and neuronal sensing; the mechano-sensing adhesion G protein-coupled receptor E2, variants of which are associated with familial vibratory urticaria; and purinergic receptors, which orchestrate tissue damage responses similarly to the IL-33 receptor. Recent evidence also points toward novel mechanisms that contribute to mast cell-mediated pathophysiology. Thus, in addition to releasing preformed mediators contained in granules and synthesizing mediators de novo, mast cells also secrete extracellular vesicles, which convey biological functions. Understanding their release, composition and uptake within a variety of clinical conditions will contribute to the understanding of disease specific pathology and likely lead the way to novel therapeutic approaches. We also discuss recent advances in the development of therapies targeting mast cell activity, including the ligation of inhibitory ITIM-containing receptors, and other strategies that suppress mast cells or responses to mediators for the management of mast cell-related diseases.
肥大细胞是组织驻留的免疫细胞，在过敏炎症的启动和持续中发挥关键作用，通常通过 IgE 介导的机制。然而，肥大细胞是进化上古老的免疫细胞，可以追溯到尾索动物，并且在 IgE 抗体出现之前，这表明它们参与了非抗体依赖的生物学功能，其中许多功能仍在研究中。本文总结了近年来对肥大细胞在健康和疾病中的作用的理解进展，部分是通过研究新兴的非 IgE 受体，如 Mas 相关 G 蛋白偶联受体 X2，该受体参与假性过敏反应以及先天防御和神经元感应；机械感应黏附 G 蛋白偶联受体 E2，其变体与家族性振动性荨麻疹有关；以及嘌呤能受体，它们类似地协调组织损伤反应。最近的证据也指向了有助于肥大细胞介导的病理生理学的新机制。因此，除了释放预先形成的颗粒中的介质和从头合成介质外，肥大细胞还分泌细胞外囊泡，这些囊泡传递生物学功能。了解它们在各种临床情况下的释放、组成和摄取将有助于了解疾病的特定病理学，并可能为新的治疗方法开辟道路。我们还讨论了靶向肥大细胞活性的治疗方法的最新进展，包括抑制性含有 ITIM 的受体的连接，以及其他抑制肥大细胞或对介质反应的策略，以管理与肥大细胞相关的疾病。
