期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 148, 期 3, 页码 799-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2021.02.018
关键词
Atopic dermatitis; basophils; M2; macrophages; efferocytosis; type 2 inflammation; resolution; IL-4; M-CSF
资金
- Health Research Council of New Zealand
- Marjorie Barclay Trust
- National Institutes of Health [AG045040]
- Welch Foundation [AQ-1507]
The study found that basophils play a key role in both promoting skin inflammation and participating in the resolution of inflammation in an AD model. Basophils and IL-4 promote epidermal hyperplasia and skin barrier dysfunction by acting on keratinocyte differentiation. They also inhibit the accumulation of proinflammatory cells in the skin while promoting the expansion and function of proresolution M2-like macrophages.
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. (J Allergy Clin Immunol 2021;148:799-812.)
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