Therapeutic and prophylactic deletion of IL-4R$α$-signaling ameliorates established ovalbumin induced allergic asthma. Khumalo, J., Kirstein, F., Scibiorek, M., Hadebe, S., & Brombacher, F. Allergy, 75(6):1347–1360, 2020. ![Therapeutic and prophylactic deletion of IL-4R$α$-signaling ameliorates established ovalbumin induced allergic asthma [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Abstract Background Allergic asthma is a chronic inflammatory airway disease driven predominantly by a TH2 immune response to environmental allergens. IL-4R$α$-signaling is essential for driving TH2-type immunity to allergens. Anti-TH2 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 if IL-4R$α$ disruption in systemically sensitised mice can prevent the onset of the disease. Methods We used RosacreERT2IL-4R$α$-/lox mice, a tamoxifen (TAM) inducible IL-4R$α$ 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$α$ demonstrated therapeutic effects, on established allergic airway disease and prevented the development of ovalbumin-induced airway hyperreactivity, eosinophilia and goblet cell metaplasia in allergen-sensitised mice. Interestingly, IL-4R$α$ knockdown after allergic sensitisation did not induce TH17, a neutrophilic inflammatory response as observed in global IL-4R$α$-deficient mice after intranasal allergen challenge. Conclusion Abrogation of IL-4R$α$ signaling after allergic sensitisation would have significant therapeutic benefit for TH2-type allergic asthma.
@article{doi:10.1111/all.14137,
abstract = {Abstract Background Allergic asthma is a chronic inflammatory airway disease driven predominantly by a TH2 immune response to environmental allergens. IL-4R$\alpha$-signaling is essential for driving TH2-type immunity to allergens. Anti-TH2 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 if IL-4R$\alpha$ disruption in systemically sensitised mice can prevent the onset of the disease. Methods We used RosacreERT2IL-4R$\alpha$-/lox mice, a tamoxifen (TAM) inducible IL-4R$\alpha$ 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$\alpha$ demonstrated therapeutic effects, on established allergic airway disease and prevented the development of ovalbumin-induced airway hyperreactivity, eosinophilia and goblet cell metaplasia in allergen-sensitised mice. Interestingly, IL-4R$\alpha$ knockdown after allergic sensitisation did not induce TH17, a neutrophilic inflammatory response as observed in global IL-4R$\alpha$-deficient mice after intranasal allergen challenge. Conclusion Abrogation of IL-4R$\alpha$ signaling after allergic sensitisation would have significant therapeutic benefit for TH2-type allergic asthma.},
author = {Khumalo, Jermaine and Kirstein, Frank and Scibiorek, Martyna and Hadebe, Sabelo and Brombacher, Frank},
doi = {10.1111/all.14137},
journal = {Allergy},
keywords = {AHR,ERT2,IL-4R$\alpha$ signaling,OA,TH2 type asthma,fund{\_}ack,original,prophylactic,tamoxifen,therapeutic},
mendeley-tags = {OA,fund{\_}ack,original},
number = {6},
pages = {1347--1360},
pmid = {31782803},
title = {{Therapeutic and prophylactic deletion of IL-4R$\alpha$-signaling ameliorates established ovalbumin induced allergic asthma}},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/all.14137},
volume = {75},
year = {2020}
}
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Methods We used RosacreERT2IL-4R$α$-/lox mice, a tamoxifen (TAM) inducible IL-4R$α$ 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$α$ demonstrated therapeutic effects, on established allergic airway disease and prevented the development of ovalbumin-induced airway hyperreactivity, eosinophilia and goblet cell metaplasia in allergen-sensitised mice. Interestingly, IL-4R$α$ knockdown after allergic sensitisation did not induce TH17, a neutrophilic inflammatory response as observed in global IL-4R$α$-deficient mice after intranasal allergen challenge. Conclusion Abrogation of IL-4R$α$ signaling after allergic sensitisation would have significant therapeutic benefit for TH2-type allergic asthma.","author":[{"propositions":[],"lastnames":["Khumalo"],"firstnames":["Jermaine"],"suffixes":[]},{"propositions":[],"lastnames":["Kirstein"],"firstnames":["Frank"],"suffixes":[]},{"propositions":[],"lastnames":["Scibiorek"],"firstnames":["Martyna"],"suffixes":[]},{"propositions":[],"lastnames":["Hadebe"],"firstnames":["Sabelo"],"suffixes":[]},{"propositions":[],"lastnames":["Brombacher"],"firstnames":["Frank"],"suffixes":[]}],"doi":"10.1111/all.14137","journal":"Allergy","keywords":"AHR,ERT2,IL-4R$α$ signaling,OA,TH2 type asthma,fund_ack,original,prophylactic,tamoxifen,therapeutic","mendeley-tags":"OA,fund_ack,original","number":"6","pages":"1347–1360","pmid":"31782803","title":"Therapeutic and prophylactic deletion of IL-4R$α$-signaling ameliorates established ovalbumin induced allergic asthma","url":"https://onlinelibrary.wiley.com/doi/abs/10.1111/all.14137","volume":"75","year":"2020","bibtex":"@article{doi:10.1111/all.14137,\r\nabstract = {Abstract Background Allergic asthma is a chronic inflammatory airway disease driven predominantly by a TH2 immune response to environmental allergens. IL-4R$\\alpha$-signaling is essential for driving TH2-type immunity to allergens. Anti-TH2 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 if IL-4R$\\alpha$ disruption in systemically sensitised mice can prevent the onset of the disease. Methods We used RosacreERT2IL-4R$\\alpha$-/lox mice, a tamoxifen (TAM) inducible IL-4R$\\alpha$ 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$\\alpha$ demonstrated therapeutic effects, on established allergic airway disease and prevented the development of ovalbumin-induced airway hyperreactivity, eosinophilia and goblet cell metaplasia in allergen-sensitised mice. Interestingly, IL-4R$\\alpha$ knockdown after allergic sensitisation did not induce TH17, a neutrophilic inflammatory response as observed in global IL-4R$\\alpha$-deficient mice after intranasal allergen challenge. 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