Basophils promote barrier dysfunction and resolution in the atopic skin

J Allergy Clin Immunol. 2021 Sep;148(3):799-812.e10. doi: 10.1016/j.jaci.2021.02.018. Epub 2021 Mar 2.


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.

Keywords: Atopic dermatitis; IL-4; M-CSF; M2; basophils; efferocytosis; macrophages; resolution; type 2 inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basophils / immunology*
  • Calcitriol / analogs & derivatives
  • Cell Differentiation
  • Cytokines / genetics
  • Cytokines / immunology
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / pathology
  • Diphtheria Toxin
  • Edema / chemically induced
  • Edema / immunology
  • Eosinophils / immunology
  • Female
  • Gene Expression
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Hyperplasia / immunology
  • Keratinocytes / cytology
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Skin / immunology*
  • Skin / pathology


  • Cytokines
  • Diphtheria Toxin
  • Histocompatibility Antigens Class II
  • calcipotriene
  • Calcitriol