Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by FcεRIβ and the Potential Impact of FcεRIβ Splicing in Allergic Inflammation.
Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by FcεRIβ and the Potential Impact of FcεRIβ Splicing in Allergic Inflammation.
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DOI：
10.3390/ijms23020788
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发表时间：
2022-01-12
影响因子：
5.6
通讯作者：
Cruse G
中科院分区：
文献类型：
--
作者：
Arthur GK;Cruse G
肥大细胞是组织驻留免疫细胞，其通过释放预先形成的颗粒储存介质和新产生的促炎介质在先天性和适应性免疫中起作用，所述促炎介质有助于过敏性炎症反应的早期和晚期的产生。虽然肥大细胞可以被激活的介质，以促进稳态和病理生理在不同的设置和背景下，在这篇综述中，我们将集中在IgE介导的激活和过敏性炎症的典型设置。肥大细胞的IgE依赖性活化通过高亲和力IgE受体FcεRI发生，FcεRI是一种多聚体受体复合物，一旦与抗原交联，就会触发信号级联反应，从而在肥大细胞中产生强大的反应。本文讨论了FcεRI的结构和功能，并描述了FcεRI β亚基（FcεRIβ）在调节肥大细胞功能和FcεRI运输和信号转导中的作用。我们讨论了目前靶向IgE和FcεRI信号传导的方法以及可以特异性靶向FcεRIβ的新兴方法。我们研究了FcεRIβ的选择性剪接如何改变蛋白质功能，以及如何将剪接操作用作治疗方法。直接靶向FcεRI和/或IgE与FcεRI结合是治疗过敏性炎症的有希望的方法。FcεRIβ在FcεRI受体复合物的运输和信号传导中的特征性作用、对IgE介导的活化途径的特异性以及在肥大细胞和嗜碱性粒细胞中的优先表达，使得FcεRIβ成为过敏和哮喘治疗策略的优秀但具有挑战性的候选者，如果靶向能够实现的话。
Mast cells are tissue-resident immune cells that function in both innate and adaptive immunity through the release of both preformed granule-stored mediators, and newly generated proinflammatory mediators that contribute to the generation of both the early and late phases of the allergic inflammatory response. Although mast cells can be activated by a vast array of mediators to contribute to homeostasis and pathophysiology in diverse settings and contexts, in this review, we will focus on the canonical setting of IgE-mediated activation and allergic inflammation. IgE-dependent activation of mast cells occurs through the high affinity IgE receptor, FcεRI, which is a multimeric receptor complex that, once crosslinked by antigen, triggers a cascade of signaling to generate a robust response in mast cells. Here, we discuss FcεRI structure and function, and describe established and emerging roles of the β subunit of FcεRI (FcεRIβ) in regulating mast cell function and FcεRI trafficking and signaling. We discuss current approaches to target IgE and FcεRI signaling and emerging approaches that could target FcεRIβ specifically. We examine how alternative splicing of FcεRIβ alters protein function and how manipulation of splicing could be employed as a therapeutic approach. Targeting FcεRI directly and/or IgE binding to FcεRI are promising approaches to therapeutics for allergic inflammation. The characteristic role of FcεRIβ in both trafficking and signaling of the FcεRI receptor complex, the specificity to IgE-mediated activation pathways, and the preferential expression in mast cells and basophils, makes FcεRIβ an excellent, but challenging, candidate for therapeutic strategies in allergy and asthma, if targeting can be realized.
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影响因子：
14.2
作者：
Ashmole, Ian;Duffy, S. Mark;Leyland, Mark L.;Morrison, Valerie S.;Begg, Malcolm;Bradding, Peter
通讯作者：
Bradding, Peter
影响因子：
3.5
作者：
Adra, CN;Mao, XQ;Hopkin, JM
通讯作者：
Hopkin, JM
DOI：
10.1038/nrm.2017.27
发表时间：
2017-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Baralle FE;Giudice J
通讯作者：
Giudice J
影响因子：
5.6
作者：
Eggel, Alexander;Baumann, Michael J.;Vogel, Monique
通讯作者：
Vogel, Monique
影响因子：
32.4
作者：
Donnadieu, E;Jouvin, MH;Kinet, JP
通讯作者：
Kinet, JP