Khumalo, JKirstein, FScibiorek, MHadebe, SBrombacher, F2024-08-112024-08-112019-11-29Khumalo J, Kirstein F, Scibiorek M, Hadebe S, Brombacher F. Therapeutic and prophylactic deletion of IL-4Ra-signaling ameliorates established ovalbumin induced allergic asthma. Allergy. 2020 Jun;75(6):1347-1360. doi: 10.1111/all.14137.https://doi.org/10.1111/all.14137https://pubmed.ncbi.nlm.nih.gov/31782803/https://hdl.handle.net/11288/597141Background: Allergic asthma is a chronic inflammatory airway disease driven predominantly by a TH 2 immune response to environmental allergens. IL-4Rα-signaling is essential for driving TH 2-type immunity to allergens. Anti-TH 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 RosacreERT2 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 TH 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 TH 2-type allergic asthma.enAttribution 3.0 United Stateshttp://creativecommons.org/licenses/by/3.0/us/IL-4RαTH2 typeProphylacticTamoxifenTherapeuticArticleAllergy