Liu Yan-Jun, Wang Hui-Ying, Wang Ran, Yu Jing, Shi Jin-Jin, Chen Ru-Yi, Yang Guan-Jun, Chen Jiong
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, School of Marine Sciences, Ningbo University, Ningbo 315211, China; Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Meishan Campus, Ningbo University, Ningbo 315832, China.
Department of Allergy and Clinical Immunology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310009, China.
Int J Biol Macromol. 2025 Jan;284(Pt 1):138099. doi: 10.1016/j.ijbiomac.2024.138099. Epub 2024 Nov 26.
In the last decade, research has clarified the binding interactions between immunoglobulin E (IgE) and its high-affinity receptor, the FcεRI alpha chain (FcεRI). The formation of the IgE-FcεRI complex is crucial in the context of atopic allergies, linking allergen recognition to cellular activation and disease manifestation. Consequently, pharmacological strategies that disrupt these interactions are vital for managing atopic conditions. Historically, the complexity of the IgE-FcεRI binding process and challenges in producing functional recombinant derivatives has complicated data interpretation. However, advancements in structural biology, protein engineering, and immunological studies have enhanced our understanding of these protein-protein interactions (PPI), facilitating the development of more effective therapies. The introduction of anti-IgE therapies underscores the significance of the IgE-FcεRI PPI in allergic asthma. IgE, that is present locally and systemically, serves as a sensory mechanism in the adaptive immune response, particularly in mast cells (MCs) and basophils. When bound to FcεRI, IgE enables rapid memory responses to allergens, but dysregulation can lead to severe allergic asthma. Thus, the reactivity of IgE sensors can be finely modulated using various IgE-associated molecules. This review explores the mechanisms underlying IgE-dependent MC activation and its regulation by these molecules, including the latest therapeutic candidates under investigation.
在过去十年中，研究已经阐明了免疫球蛋白E（IgE）与其高亲和力受体FcεRIα链（FcεRI）之间的结合相互作用。IgE-FcεRI复合物的形成在特应性过敏的背景下至关重要，它将过敏原识别与细胞活化和疾病表现联系起来。因此，破坏这些相互作用的药理学策略对于控制特应性疾病至关重要。从历史上看，IgE-FcεRI结合过程的复杂性以及生产功能性重组衍生物的挑战使数据解释变得复杂。然而，结构生物学、蛋白质工程和免疫学研究的进展增强了我们对这些蛋白质-蛋白质相互作用（PPI）的理解，促进了更有效疗法的开发。抗IgE疗法的引入凸显了IgE-FcεRI PPI在过敏性哮喘中的重要性。局部和全身存在的IgE在适应性免疫反应中作为一种传感机制，特别是在肥大细胞（MCs）和嗜碱性粒细胞中。当与FcεRI结合时，IgE能够对过敏原产生快速的记忆反应，但调节异常会导致严重的过敏性哮喘。因此，可以使用各种与IgE相关的分子来精细调节IgE传感器的反应性。本综述探讨了IgE依赖性MC活化的潜在机制及其受这些分子的调节，包括正在研究的最新治疗候选物。
