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首页> 外文期刊>Allergy >Therapeutic and prophylactic deletion of IL‐4Ra‐signaling ameliorates established ovalbumin induced allergic asthma
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Therapeutic and prophylactic deletion of IL‐4Ra‐signaling ameliorates established ovalbumin induced allergic asthma

机译：IL-4ra信号传导的治疗和预防性缺失是建立了卵巢蛋白诱导的过敏性哮喘

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Abstract Background Allergic asthma is a chronic inflammatory airway disease driven predominantly by a T H 2 immune response to environmental allergens. IL‐4Rα‐signaling is essential for driving T H 2‐type immunity to allergens. Anti‐T H 2 therapies have the potential to effectively reduce airway obstruction and inflammation in allergic asthma. Objective We investigated potential therapeutic effects of selective inhibition of this pathway in mice with established allergic airway disease. We further investigated whether IL‐4Rα disruption in systemically sensitized mice can prevent the onset of the disease. Methods We used Rosa creERT2 IL‐4Rα ?/lox mice, a tamoxifen (TAM)‐inducible IL‐4Rα knockdown model to investigate the role of IL‐4/IL‐13 signaling prior to the onset of the disease and during the effector phase in the ovalbumin‐induced allergic airway disease. Results Inducible deletion of IL‐4Rα demonstrated therapeutic effects, on established allergic airway disease, and prevented the development of ovalbumin‐induced airway hyperreactivity, eosinophilia, and goblet cell metaplasia in allergen‐sensitized mice. Interestingly, IL‐4Rα knockdown after allergic sensitization did not induce T H 17, a neutrophilic inflammatory response as observed in global IL‐4Rα‐deficient mice after intranasal allergen challenge. Conclusion Abrogation of IL‐4Rα signaling after allergic sensitization would have significant therapeutic benefit for T H 2‐type allergic asthma.
机译：摘要背景技术过敏性哮喘是一种慢性炎症气道疾病，其主要由T H 2免疫应对环境过敏原驱动。 IL-4Rα-信令对于驱动T H 2型免疫至过敏原是必不可少的。抗T H 2疗法有可能有效地降低气道阻塞和过敏性哮喘的炎症。目的我们调查了具有成熟过敏气道疾病的小鼠中该途径对小鼠的潜在治疗疗效。我们进一步研究了IL-4Rα在系统性敏化小鼠中的破坏是否可以防止疾病的发作。方法我们使用罗莎Creert2 IL-4Rαα/ Lox小鼠，一种Tamoxifen（TAM） - 剩余的IL-4Rα敲低模型，以研究IL-4 / IL-13信号传导在疾病的发作之前和效应相期间的作用在卵蛋白诱导的过敏气道疾病中。结果IL-4Rα的诱导缺失缺乏治疗效果，在已建立的过敏气道疾病中，预防过敏原致敏小鼠的卵霉素诱导的气道高反应性，嗜酸性粒细胞和脚蛋白细胞元。有趣的是，IL-4Rα在过敏性敏化后敲低在鼻内过敏原攻击后全球IL-4Rα缺陷小鼠中观察到的中性粒细胞炎症反应。结论过敏致敏后IL-4Rα信号传导对T H 2型过敏性哮喘具有显着的治疗益处。

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