IL-4R alpha signalling in B cells and T cells play differential roles in acute and chronic atopic dermatitis

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-4R alpha), an IL-4/IL-13 signalling axis, with dupilumab shows efficacy in AD. We investigated the importance of IL-4R alpha 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-4R alpha(-/lox), iLCK(cre)IL-4R alpha(-/lox), (LCKIL)-I-cre-4R alpha(-/lox), CD4(cre)IL-4R alpha(-/lox), Foxp3(cre)IL-4R alpha(-/lox) and IL-4R alpha(-/lox) littermate controls. IL-4R alpha-responsive B cells were essential in serum IgE levels, but not in epidermal thickening in both chronic and acute models. IL-4R alpha-responsive T cells were essential in epidermal thickening in the pan-T cell, but not CD4 or CD8 T cells suggesting the importance of gamma delta T cells during acute AD. Our results suggest that IL-4R alpha responsiveness on innate T cells regulates acute atopic dermatitis, while on B cells it regulates IgE.

Automated summary

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by primary skin barrier dysfunction and aberrant TH2 responses. Targeting IL-4R alpha with dupilumab shows efficacy in AD treatment. In this study, we investigated the importance of IL-4R alpha signaling in B and T cells in acute and chronic models of AD.