IL-4Rα signalling in B cells and T cells play differential roles in acute and chronic atopic dermatitis
Martyna Scibiorek, Nontobeko Mthembu, Sandisiwe Mangali, Amkele Ngomti, Paul Chukwudi Ikwegbue, Frank Brombacher, Sabelo Hadebe
Abstract
Abstract 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 mb1 cre IL-4Rα −/lox , iLCK cre IL-4Rα −/lox , LCK cre IL-4Rα −/lox , CD4 cre IL-4Rα −/lox , Foxp3 cre IL-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.