Pharmacology and Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Human Medicine, University of Oldenburg, Oldenburg, Germany.
J Allergy Clin Immunol. 2022 Jun;149(6):1833-1844. doi: 10.1016/j.jaci.2022.01.030. Epub 2022 Mar 8.
Mast cells are highly granular tissue-resident cells and key drivers of inflammation, particularly in allergies as well as in other inflammatory diseases. Most mast cell research was initially conducted in rodents but has increasingly shifted to the human system, with the advancement of research technologies and methodologies. Today we can analyze primary human cells including rare subpopulations, we can produce and maintain mast cells isolated from human tissues, and there are several human mast cell lines. These tools have substantially facilitated our understanding of their role and function in different organs in both health and disease. We can now define more clearly where human mast cells originate from, how they develop, which mediators they store, produce de novo, and release, how they are activated and by which receptors, and which neighboring cells they interact with and by which mechanisms. Considerable progress has also been made regarding the potential contribution of mast cells to disease, which, in turn, has led to the development of novel approaches for preventing key pathogenic effects of mast cells, heralding the era of mast cell-targeted therapeutics. In this review, we present and discuss a selection of some of the most significant advancements and remaining gaps in our understanding of human mast cells during the last 25 years, with a focus on clinical relevance.
肥大细胞是高度颗粒状的组织驻留细胞，是炎症的关键驱动因素，特别是在过敏以及其他炎症性疾病中。大多数肥大细胞研究最初是在啮齿动物中进行的，但随着研究技术和方法的进步，研究已经越来越多地转向人类系统。如今，我们可以分析包括稀有亚群在内的原代人类细胞，我们可以从人类组织中分离和维持肥大细胞，并且有几种人类肥大细胞系。这些工具极大地促进了我们对它们在健康和疾病状态下在不同器官中的作用和功能的理解。我们现在可以更清楚地定义人类肥大细胞的起源、它们如何发育、它们储存、从头产生和释放哪些介质、它们如何被激活以及通过哪些受体、以及它们与哪些相邻细胞相互作用以及通过哪些机制。在肥大细胞对疾病的潜在贡献方面也取得了相当大的进展，这反过来又导致了预防肥大细胞关键致病作用的新方法的发展，标志着肥大细胞靶向治疗的时代的到来。在这篇综述中，我们介绍并讨论了过去 25 年来我们对人类肥大细胞理解的一些最重要的进展和仍然存在的差距，重点是临床相关性。
