Background: Allergic asthma is a chronic inflammatory airway disease driven predominantly by a T H 2 immune response to environmental allergens. IL-4Rα-signaling is essential for driving T H 2-type immunity to allergens. Anti-T H 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 creERT2 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 T H 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 H 2-type allergic asthma. K E Y W O R D S IL-4Rα, prophylactic, tamoxifen, T H 2 type, therapeuticThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Background: B cells play an important role in allergies through secretion of IgE. IL-4 receptor a (IL-4Ra) is key in allergic asthma and regulates type 2 cytokine production, IgE secretion, and airway hyperresponsiveness. IL-4 activation of B cells is essential for class switching and contributes to the induction of B effector 2 (Be2) cells. The role of Be2 cells and signaling via IL-4Ra in B cells is not clearly defined. Objective: We sought to find out whether IL-4Ra-responsive B cells or Be2 function was essential in experimental allergic asthma.Methods: Mice lacking IL-4Ra on B cells (mb1 cre IL-4Ra 2/lox ) or littermate controls (IL-4Ra 2/lox ) and mice lacking IL-4 or IL-4/IL-13 on B cells were sensitized and challenged with highdose house dust mite (>10 mg) or with low-dose house dust mite (<3 mg). We also adoptively transferred naive IL-4Ra 2/lox or IL-4Ra 2/2 B cells into mMT 2/2 mice a day before sensitization or a day before challenge. We analyzed lung inflammation, cellular infiltrate, and airway hyperresponsiveness.