New Mechanistic Advances in FcεRI-Mast Cell-Mediated Allergic Signaling.

IF 8.4 2区 医学 Q1 ALLERGY
Clinical Reviews in Allergy & Immunology Pub Date : 2022-12-01 Epub Date: 2022-10-17 DOI:10.1007/s12016-022-08955-9
Yang Li, Patrick S C Leung, M Eric Gershwin, Junmin Song
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引用次数: 9

Abstract

Mast cells originate from the CD34+/CD117+ hematopoietic progenitors in the bone marrow, migrate into circulation, and ultimately mature and reside in peripheral tissues. Microbiota/metabolites and certain immune cells (e.g., Treg cells) play a key role in maintaining immune tolerance. Cross-linking of allergen-specific IgE on mast cells activates the high-affinity membrane-bound receptor FcεRI, thereby initiating an intracellular signal cascade, leading to degranulation and release of pro-inflammatory mediators. The intracellular signal transduction is intricately regulated by various kinases, transcription factors, and cytokines. Importantly, multiple signal components in the FcεRI-mast cell-mediated allergic cascade can be targeted for therapeutic purposes. Pharmacological interventions that include therapeutic antibodies against IgE, FcεRI, and cytokines as well as inhibitors/activators of several key intracellular signaling molecues have been used to inhibit allergic reactions. Other factors that are not part of the signal pathway but can enhance an individual's susceptibility to allergen stimulation are referred to as cofactors. Herein, we provide a mechanistic overview of the FcεRI-mast cell-mediated allergic signaling. This will broaden our scope and visions on specific preventive and therapeutic strategies for the clinical management of mast cell-associated hypersensitivity reactions.

Abstract Image

Abstract Image

fcε - ri肥大细胞介导的过敏信号转导机制的新进展
肥大细胞起源于骨髓中的CD34+/CD117+造血祖细胞,迁移到循环中,最终成熟并存在于外周组织中。微生物群/代谢物和某些免疫细胞(如Treg细胞)在维持免疫耐受方面发挥关键作用。肥大细胞上的过敏原特异性IgE交联激活高亲和的膜结合受体FcεRI,从而启动细胞内信号级联,导致脱颗粒和释放促炎介质。细胞内信号转导受多种激酶、转录因子和细胞因子的复杂调控。重要的是,fcε - ri肥大细胞介导的过敏级联中的多个信号成分可以靶向治疗。包括针对IgE、FcεRI和细胞因子的治疗性抗体以及几种关键细胞内信号分子的抑制剂/激活剂在内的药物干预已被用于抑制过敏反应。其他不属于信号通路的因素,但可以增强个体对过敏原刺激的易感性,被称为辅助因素。在此,我们提供了fcε - ri肥大细胞介导的过敏信号的机制概述。这将拓宽我们对肥大细胞相关超敏反应临床管理的具体预防和治疗策略的范围和视野。
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来源期刊
CiteScore
22.30
自引率
1.10%
发文量
58
审稿时长
6-12 weeks
期刊介绍: Clinical Reviews in Allergy & Immunology is a scholarly journal that focuses on the advancement of clinical management in allergic and immunologic diseases. The journal publishes both scholarly reviews and experimental papers that address the current state of managing these diseases, placing new data into perspective. Each issue of the journal is dedicated to a specific theme of critical importance to allergists and immunologists, aiming to provide a comprehensive understanding of the subject matter for a wide readership. The journal is particularly helpful in explaining how novel data impacts clinical management, along with advancements such as standardized protocols for allergy skin testing and challenge procedures, as well as improved understanding of cell biology. Ultimately, the journal aims to contribute to the improvement of care and management for patients with immune-mediated diseases.
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