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，通常通过 IgE 介导的机制在过敏性炎症的起始和持续中发挥关键作用。然而，肥大细胞是进化的古老免疫细胞，可以追溯到尿脊索动物和 IgE 抗体出现之前，这表明它们参与了与抗体无关的生物学功能，其中许多功能仍在研究中。在此，我们总结了了解肥大细胞在健康和疾病中的作用的最新进展，部分是通过研究新兴的非 IgE 受体，例如与假过敏反应有关的 Mas 相关 G 蛋白偶联受体 X2，以及在先天防御和神经元感知方面；机械感应粘附 G 蛋白偶联受体 E2，其变体与家族性振动性荨麻疹有关；和嘌呤能受体，其协调与 IL-33 受体相似的组织损伤反应。最近的证据还指出了有助于肥大细胞介导的病理生理学的新机制。因此，除了释放包含在颗粒中的预制介质和合成介质从头开始，肥大细胞还分泌细胞外囊泡，传递生物学功能。了解它们在各种临床条件下的释放、组成和摄取将有助于了解疾病特异性病理学，并可能为新的治疗方法开辟道路。我们还讨论了针对肥大细胞活性的疗法开发的最新进展，包括连接抑制性 ITIM 受体，以及其他抑制肥大细胞或对调节肥大细胞相关疾病的调节剂反应的策略。