Christophe, Pellefigues, Karmella, Naidoo, Palak, Mehta, Alfonso , Schmidt, Ferdinand, Jagot, Roussel, Elsa, Cait, Alissa, Bibek, Yumnam, Sally, Chappell, Meijlink, Kimberly, Mali, Chamberis, Jean, Jiang, Gavin, Painter, Filbey, Kara, Uluckan, Ozge, Olivier, Gasser and Graham, LeGros (2021) Basophils promote barrier dysfunction and resolution in the atopic skin. Journal of Allergy and Clinical Immunology. ISSN 10976825

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.

Item Type:	Article
Keywords:	Atopic dermatitis basophils efferocytosis IL-4 M-CSF M2 macrophages resolution type 2 inflammation
Date Deposited:	22 Apr 2021 00:45
Last Modified:	22 Apr 2021 00:45
URI:	https://oak.novartis.com/id/eprint/42288