Therapeutic and Prophylactic Deletion of IL-4Ra-signaling Ameliorates Established Ovalbumin Induced Allergic Asthma

Overview

Journal Allergy

Specialty Allergy & Immunology

Date 2019 Nov 30

PMID 31782803

Citations 7

Authors

Jermaine Khumalo

Frank Kirstein

Martyna Scibiorek

Sabelo Hadebe

Frank Brombacher

Affiliations

Soon will be listed here.

Abstract

Background: Allergic asthma is a chronic inflammatory airway disease driven predominantly by a T 2 immune response to environmental allergens. IL-4Rα-signaling is essential for driving T 2-type immunity to allergens. Anti-T 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 IL-4Rα 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 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 2-type allergic asthma.

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