Basophils promote barrier dysfunction and resolution in the atopic skin

ABSTRACT Background Type 2 cytokines IL-4 and IL-13 promote atopic dermatitis (AD) but also the resolution of inflammation. How type 2 cytokines participate in the resolution of AD is poorly known. Objective To determine the mechanisms and cell types governing skin inflammation, barrier dysfunction, and the resolution of inflammation in a model of atopic dermatitis (AD) Methods Mice reporting the expression of IL-4, IL-13, and MCPT8, or that could be deleted of basophils or eosinophils, or deficient in IL-4 or MHCII molecules, or in which basophils lack M-CSF, were treated with MC903 as an acute model of AD. Kinetics of the disease; keratinocyte differentiation; leukocyte accumulation, phenotype, function and cytokine production were measured by histopathology, molecular biology, or unbiased analysis of spectral flow cytometry. Results Basophils were activated systemically and were the initial and main source of IL-4 in the skin in this model of AD. Basophil and IL-4 promoted epidermal hyperplasia and skin barrier dysfunction by acting on keratinocytes differentiation during inflammation. Basophil, IL-4 and basophil derived M-CSF inhibited the accumulation of pro-inflammatory cells in the skin while promoting the expansion and function of pro-resolution M2-like macrophages and the expression of pro-barrier genes. Basophils kept their pro-resolution properties during AD resolution. Conclusion Basophils can display both beneficial and detrimental type 2 functions simultaneously during atopic inflammation.