Allergy · 2020
Therapeutic and prophylactic deletion of IL-4Ra-signaling ameliorates established ovalbumin induced allergic asthma.
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Khumalo Jermaine, Kirstein Frank, Scibiorek Martyna, Hadebe Sabelo, Brombacher Frank
Аннотация
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.
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.