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

Audrey Progneaux, Celine Evrard, Valerie De Glas, Alix Fontaine, Evelyne DE VUYST, Arjen F. Nikkels, Vicente Garcia-Gonzalez, Laure Dumoutier, Catherine Lambert De Rouvroit, Yves Poumay

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)660-670
Number of pages11
JournalExperimental dermatology
Volume32
Issue number5
Early online date19 Jan 2023
DOIs
Publication statusPublished - May 2023

Keywords

  • atopic dermatitis
  • barrier function
  • interleukins
  • keratinocyte biology
  • Signal Transduction.

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