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食物过敏中的肥大细胞:引发即刻反应并塑造长期免疫。

Mast cells in food allergy: Inducing immediate reactions and shaping long-term immunity.

作者信息

Oettgen Hans C

机构信息

Department of Pediatrics, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass.

出版信息

J Allergy Clin Immunol. 2023 Jan;151(1):21-25. doi: 10.1016/j.jaci.2022.10.003. Epub 2022 Nov 1.

Abstract

Mast cells are distributed throughout the gastrointestinal tract and function as the main effector cells of IgE-mediated allergic reactions to foods. Allergen-induced cross-linking of IgE antibodies bound to high-affinity IgE receptors, FcεRI, on the surface of mast cells triggers their activation, resulting in the release of mediators of immediate hypersensitivity. These mediators rapidly induce both local gastrointestinal and systemic physiological responses including anaphylaxis. Emerging evidence has revealed that, in addition to inciting immediate reactions, mast cells are key regulators of adaptive immunity to foods. In the gastrointestinal mucosa they provide the priming cytokines that initiate and, over time, consolidate adaptive T2 responses to ingested allergens as well as TNF and chemokines that orchestrate the recruitment of tissue-infiltrating leukocytes that drive type 2 tissue inflammation. Patients with atopic dermatitis have increased intestinal mast cell numbers and are at a greater risk for food allergy. Recent studies have uncovered a skin-gut axis in which epicutaneous allergen exposure drives intestinal mast cell expansion. The activating effects of IgE antibodies in mast cells are countered by food-specific IgG antibodies that signal via the inhibitory IgG receptor, FcγR2b, suppressing both immediate allergic reactions to foods and the type 2 immune adjuvant activity of mast cells.

摘要

肥大细胞分布于整个胃肠道,是IgE介导的食物过敏反应的主要效应细胞。变应原诱导与肥大细胞表面高亲和力IgE受体FcεRI结合的IgE抗体发生交联,触发其活化,导致速发型超敏反应介质的释放。这些介质迅速诱导局部胃肠道和全身生理反应,包括过敏反应。新出现的证据表明,除了引发即时反应外,肥大细胞还是食物适应性免疫的关键调节因子。在胃肠道黏膜中,它们提供启动并随着时间巩固对摄入变应原的适应性T2反应的起始细胞因子,以及协调驱动2型组织炎症的组织浸润白细胞募集的肿瘤坏死因子(TNF)和趋化因子。特应性皮炎患者的肠道肥大细胞数量增加,发生食物过敏的风险更高。最近的研究发现了一个皮肤-肠道轴,其中经皮暴露变应原会驱动肠道肥大细胞扩增。肥大细胞中IgE抗体的活化作用可被食物特异性IgG抗体抵消,后者通过抑制性IgG受体FcγR2b发出信号,抑制对食物的即时过敏反应以及肥大细胞的2型免疫佐剂活性。

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