Immunoallergology Unit, Department of Clinical and Experimental Medicine, Pisa University, Pisa, Italy.
Immunoallergology Unit, Department of Clinical and Experimental Medicine, Pisa University, Pisa, Italy.
Ann Allergy Asthma Immunol. 2024 Oct;133(4):374-379. doi: 10.1016/j.anai.2024.04.023. Epub 2024 Apr 23.
Chronic urticaria is a mast cell (MC)-driven disease characterized by the development of itching wheals and/or angioedema. In the last decades, outstanding progress has been made in defining the mechanisms involved in MC activation, and novel activating and inhibitory receptors expressed in MC surface were identified and characterized. Besides an IgE-mediated activation through high-affinity IgE receptor cross-linking, other activating receptors, including Mas-related G-protein-coupled receptor-X2, C5a receptor, and protease-activated receptors 1 and 2 are responsible for MC activation. This would partly explain the reason some subgroups of chronic spontaneous urticaria (CSU), the most frequent form of urticaria in the general population, do not respond to IgE target therapies, requiring other therapeutic approaches for improving the management of the disease. In this review, we shed some light on the current knowledge of the immunologic and nonimmunologic mechanisms regulating MC activation in CSU, considering the complex inflammatory scenario underlying CSU pathogenesis, and novel potential MC-targeted therapies, including surface receptors and cytoplasmic signaling proteins.
慢性荨麻疹是一种肥大细胞(MC)驱动的疾病,其特征是出现瘙痒性风团和/或血管性水肿。在过去的几十年中,人们在定义 MC 激活所涉及的机制方面取得了杰出的进展,并鉴定和表征了在 MC 表面表达的新型激活和抑制受体。除了通过高亲和力 IgE 受体交联进行 IgE 介导的激活外,其他激活受体,包括 Mas 相关 G 蛋白偶联受体-X2、C5a 受体和蛋白酶激活受体 1 和 2,也负责 MC 的激活。这部分解释了为什么某些慢性自发性荨麻疹(CSU)亚组,即普通人群中最常见的荨麻疹形式,对 IgE 靶向治疗无反应,需要其他治疗方法来改善疾病的管理。在这篇综述中,我们探讨了调节 CSU 中 MC 激活的免疫和非免疫机制的最新知识,同时考虑了 CSU 发病机制背后复杂的炎症情况以及新型潜在的针对 MC 的治疗方法,包括表面受体和细胞质信号蛋白。