Keratinocytes activated by IL‐4/IL‐13 express IL‐2Rγ with consequences on epidermal barrier function. Issue 5 (26th January 2023) - Progneaux, Audrey
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. Abstract : Epidermal keratinocytes start expressing IL‐2Rγ and IL‐13Rα2 after activation of type II IL‐4Rα/IL‐13Rα1 receptor by IL‐4 and IL‐13. Data indicate that expression of the IL‐2Rγ receptor subunit participate to the barrier alteration produced by both interleukins. They also show that expression of IL‐2Rγ controls expression of IL‐13Rα2.