Keratinocytes activated by IL-4/IL-13 express IL-2Rγ with consequences on epidermal barrier function

Atopic dermatitis (AD) is a Th2-type inflammatory disease characterized by an alteration of epidermal barrier following the release of IL-4 and IL-13. These cytokines activate type II IL-4Rα/IL-13Rα1 receptors in the keratinocyte. Whilst IL-2Rγ, that forms type I receptor for IL-4, is only expressed in haematopoietic cells, recent studies suggest its induction in keratinocytes, which questions about its role. We studied expression of IL-2Rγ in keratinocytes and its role in alteration of keratinocyte function and epidermal barrier. IL-2Rγ expression in keratinocytes was studied using both reconstructed human epidermis (RHE) exposed to IL-4/IL-13 and AD skin. IL-2Rγ induction by type II receptor has been analyzed using JAK inhibitors and RHE knockout (KO) for IL13RA1. IL-2Rγ function was investigated in RHE KO for IL2RG. In RHE, IL-4/IL-13 induce expression of IL-2Rγ at the mRNA and protein levels. Its mRNA expression is also visualized in keratinocytes of lesional AD skin. IL-2Rγ expression is low in RHE treated with JAK inhibitors and absent in RHE KO for IL13RA1. Exposure to IL-4/IL-13 alters epidermal barrier, but this alteration is absent in RHE KO for IL2RG. A more important induction of IL-13Rα2 is reported in RHE KO for IL2RG than in not edited RHE. These results demonstrate IL-2Rγ induction in keratinocytes through activation of type II receptor. IL-2Rγ is involved in the alteration of the epidermal barrier and in the regulation of IL-13Rα2 expression. Observation of IL-2Rγ expression by keratinocytes inside AD lesional skin suggests a role for this receptor subunit in the disease.

Disciplines :

Dermatology

Author, co-author :

Progneaux, Audrey

Evrard, Céline ; Université de Liège - ULiège > Chimie et bio-industries > Chimie biologique industrielle

De Glas, Valérie

Fontaine, Alix

Dotreppe, Céline

De Vuyst, Evelyne

Nikkels, Arjen ; Centre Hospitalier Universitaire de Liège - CHU > > Service de dermatologie

Garcia-Gonzalez, Vicente

Dumoutier, Laure

Lambert de Rouvroit, Catherine

Poumay, Yves

Language :

English

Title :

Keratinocytes activated by IL-4/IL-13 express IL-2Rγ with consequences on epidermal barrier function

Publication date :

2023

Journal title :

Experimental Dermatology

ISSN :

0906-6705

eISSN :

1600-0625

Publisher :

Blackwell, Oxford, United Kingdom

Available on ORBi :

since 03 May 2023

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