IL-13 overexpression predisposes to anaphylaxis following antigen sensitization
IL-13 overexpression predisposes to anaphylaxis following antigen sensitization
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DOI：
10.4049/jimmunol.166.4.2712
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发表时间：
2001-02-15
影响因子：
4.4
通讯作者：
McKenzie, ANJ
中科院分区：
文献类型：
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作者：
Fallon, PG;Emson, CL;McKenzie, ANJ
过敏反应是过敏反应的一种极端形式。过敏和哮喘的这种急性期成分是由过敏原诱导的肥大细胞脱粒引发的，随后细胞表面结合的过敏原特异性 IgE 交联，导致炎症介质的释放和支气管收缩的发展。我们使用 IL-13 转基因小鼠来研究这种 Th2 细胞衍生的细胞因子在过敏性疾病发作中的作用。引人注目的是，IL-13 转基因小鼠在 Ag 致敏后极易发生致命的过敏反应。这种反应与循环中 Ag 特异性 IgE、肥大细胞脱颗粒和组胺释放水平的大幅升高相关。此外，过敏原暴露还会诱发哮喘典型的表型变化，包括肺纤维化、杯状细胞增生、Th2细胞因子升高、嗜酸性粒细胞增多以及气道被粘液和Charcot-Leyden晶体堵塞。 IgE 介导的反应的诱导不需要 IL-4 的表达。这些数据首次表征了 IL-U 诱导的 IgE 在立即超敏反应产生中的功能作用，并强调了 IL-13 在特应性症状发展中的重要性。这种反应的系统调节使这些小鼠成为研究特应性反应的重要资源，
Anaphylaxis represents an extreme form of allergic reaction. This acute-phase component of allergy and asthma is triggered by allergen-induced degranulation of mast cells following the cross-linking of cell surface-bound, allergen-specific IgE, resulting in the liberation of inflammatory: mediators and the development of bronchoconstriction. We used IL-13 transgenic mice to investigate the role of this Th2 cell-derived cytokine in the onset of allergic disease. Strikingly, IL-13-transgenic mise were highly predisposed to fatal anaphylaxis following Ag sensitization. This response correlated with substantially elevated levels of circulating Ag-specific IgE, mast cell degranulation, and histamine release. Furthermore, allergen exposure also induced phenotypic changes typical of asthma, including pulmonary fibrosis, goblet cell hyperplasia, elevated Th2 cytokines, eosinophilia, and airways occluded by mucus and Charcot-Leyden crystals. Expression of IL-4 was not required for the induction of IgE-mediated responses. These data represent the first characterization of a functional role for IL-U-induced IgE in the generation of immediate hypersensitivity reactions and highlight the importance of IL-13 in the development of the symptoms of atopy. The systemic regulation of this response makes these mice an important resource for studying atopic responses,