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Publication: Therapeutic and prophylactic deletion of IL-4Rα-signaling ameliorates established ovalbumin induced allergic asthma
Khumalo, J Kirstein, F Scibiorek, M Hadebe, S Brombacher, F
Khumalo, J
Kirstein, F
Scibiorek, M
Hadebe, S
Brombacher, F
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Abstract
Background: 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.
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Date
2019-11-29
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Publisher
Wiley
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Keywords
IL-4Rα,TH2 type,Prophylactic,Tamoxifen,Therapeutic
Citation
Khumalo 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.