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

First Author  Scibiorek M Year  2023
Journal  Sci Rep Volume  13
Issue  1 Pages  144
PubMed ID  36599893 Mgi Jnum  J:351828
Mgi Id  MGI:7424312 Doi  10.1038/s41598-022-26637-6
Citation  Scibiorek M, et al. (2023) IL-4Ralpha signalling in B cells and T cells play differential roles in acute and chronic atopic dermatitis. Sci Rep 13(1):144
abstractText  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-4Ralpha), an IL-4/IL-13 signalling axis, with dupilumab shows efficacy in AD. We investigated the importance of IL-4Ralpha 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-4Ralpha(-/lox), iLCK(cre)IL-4Ralpha(-/lox), LCK(cre)IL-4Ralpha(-/lox), CD4(cre)IL-4Ralpha(-/lox), Foxp3(cre)IL-4Ralpha(-/lox) and IL-4Ralpha(-/lox) littermate controls. IL-4Ralpha-responsive B cells were essential in serum IgE levels, but not in epidermal thickening in both chronic and acute models. IL-4Ralpha-responsive T cells were essential in epidermal thickening in the pan-T cell, but not CD4 or CD8 T cells suggesting the importance of gammadeltaT cells during acute AD. Our results suggest that IL-4Ralpha responsiveness on innate T cells regulates acute atopic dermatitis, while on B cells it regulates IgE.
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