Abstract
Background: The type 2 cytokines IL-4 and IL-13 promote not only atopic dermatitis (AD) but also the resolution of inflammation. How type 2 cytokines participate in the resolution of AD is poorly known. Objective: Our aim was to determine the mechanisms and cell types governing skin inflammation, barrier dysfunction, and resolution of inflammation in a model of AD. Methods: Mice that exhibit expression of IL-4, IL-13, and MCPT8 or that could be depleted of basophils or eosinophils, be deficient in IL-4 or MHC class II molecules, or have basophils lacking macrophage colony-stimulating factor (M-CSF) were treated with calcipotriol (MC903) as an acute model of AD. Kinetics of the disease; keratinocyte differentiation; and leukocyte accumulation, phenotype, function, and cytokine production were measured by transepidermal water loss, histopathology, molecular biology, or unbiased analysis of spectral flow cytometry. Results: In this model of AD, basophils were activated systemically and were the initial and main source of IL-4 in the skin. Basophils and IL-4 promoted epidermal hyperplasia and skin barrier dysfunction by acting on keratinocyte differentiation during inflammation. Basophils, IL-4, and basophil-derived M-CSF inhibited the accumulation of proinflammatory cells in the skin while promoting the expansion and function of proresolution M2-like macrophages and the expression of probarrier genes. Basophils kept their proresolution properties during AD resolution. Conclusion: Basophils can display both beneficial and detrimental type 2 functions simultaneously during atopic inflammation.
Original language | English (US) |
---|---|
Pages (from-to) | 799-812.e10 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 148 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2021 |
Keywords
- Atopic dermatitis
- IL-4
- M-CSF
- M2
- basophils
- efferocytosis
- macrophages
- resolution
- type 2 inflammation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology