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

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 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.

Exploring the Potential of IL-4 and IL-13 Plasma Levels as Biomarkers in Atopic Dermatitis

“…The IL-22 serum levels correlated much better with the clinical improvement of the Dupilumab-treated patients. Several studies reported similar results, suggesting that IL-22 might be a potential reliable biomarker [ 21 , 22 , 23 ].…”

Prevention of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linnén on cutaneous squamous cell carcinomas progression following UV irradiation in mice

“…In addition, the present study evaluated the expression levels of CD11b, which is commonly used as a biomarker for NK cells, monocytes, dendritic cells and neutrophils (77)(78)(79)(80). B cells and T cells are also important classes of immune cells that serve an important role in skin inflammation and skin cancer progression (81,82). In future studies, the relationship between T cells and B cells and the progression of skin cancer should be examined.…”

Effects of tyndallized lactic acid bacteria separated from Phellinus linteus on inflammation and skin barrier damage induced by DNCB

“…In AD, Th2 cells primarily secrete IL-4 and IL-5, which stimulate B cells to produce IgE, in uencing the levels of IgG1 and IgG2a, as well as the production of various in ammatory cytokines [35]. IgE levels also play a role in sensitizing allergens [36,37].…”