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.

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with complex environmental and genetic predisposing factors. Primary skin barrier dysfunction and aberrant T helper 2 (TH2) responses to common allergens, together with increased serum IgE antibodies, characterise the disease. B and T cells are essential in the disease manifestation, however, the exact mechanism of how these cells is involved is unclear. Targeting interleukin 4 receptor alpha (IL-4Rα), an IL-4/IL-13 signalling axis, with dupilumab shows efficacy in AD. We investigated the importance of IL-4Rα signalling specifically on B and T cells during acute and chronic models of AD. We used House dust mite (HDM) and Ovalbumin (OVA) in chronic models and a low-calcemic analog of vitamin D (MC903) for acute models of AD. We used mb1creIL-4Rα−/lox, iLCKcreIL-4Rα−/lox, LCKcreIL-4Rα−/lox, CD4creIL-4Rα−/lox, Foxp3creIL-4Rα−/lox and IL-4Rα−/lox littermate controls. IL-4Rα-responsive B cells were essential in serum IgE levels, but not in epidermal thickening in both chronic and acute models. IL-4Rα-responsive T cells were essential in epidermal thickening in the pan-T cell, but not CD4 or CD8 T cells suggesting the importance of γδT cells during acute AD. Our results suggest that IL-4Rα responsiveness on innate T cells regulates acute atopic dermatitis, while on B cells it regulates IgE.