Therapeutic And Prophylactic Deletion Of Il-4r Alpha Signaling Ameliorates Established Ovalbumin-Induced Allergic Asthma
ALLERGY(2020)
摘要
Background Allergic asthma is a chronic inflammatory airway disease driven predominantly by a T(H)2 immune response to environmental allergens. IL-4R alpha-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-4R alpha disruption in systemically sensitized mice can prevent the onset of the disease. Methods We used Rosa(creERT2)IL-4R alpha(-/lox) mice, a tamoxifen (TAM)-inducible IL-4R alpha 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-4R alpha 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-4R alpha knockdown after allergic sensitization did not induce T(H)17, a neutrophilic inflammatory response as observed in global IL-4R alpha-deficient mice after intranasal allergen challenge. Conclusion Abrogation of IL-4R alpha signaling after allergic sensitization would have significant therapeutic benefit for T(H)2-type allergic asthma.
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关键词
IL-4R alpha, prophylactic, tamoxifen, T(H)2 type, therapeutic
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