Therapeutic and prophylactic deletion of IL-4Ra-signaling ameliorates established ovalbumin induced allergic asthma.

ABSTRACT: BACKGROUND:Allergic asthma is a chronic inflammatory airway disease driven predominantly by a TH 2 immune response to environmental allergens. IL-4R?-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-4R? disruption in systemically sensitized mice can prevent the onset of the disease. METHODS:We used RosacreERT2 IL-4R?-/lox mice, a tamoxifen (TAM)-inducible IL-4R? 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? 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? knockdown after allergic sensitization did not induce TH 17, a neutrophilic inflammatory response as observed in global IL-4R?-deficient mice after intranasal allergen challenge. CONCLUSION:Abrogation of IL-4R? signaling after allergic sensitization would have significant therapeutic benefit for TH 2-type allergic asthma.

SUBMITTER: Khumalo J 

PROVIDER: S-EPMC7318634 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature