Basophils promote barrier dysfunction and resolution in the atopic skin.
J Allergy Clin Immunol
; 148(3): 799-812.e10, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-33662369
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piel
/
Basófilos
/
Dermatitis Atópica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2021
Tipo del documento:
Article