Keratinocytes activated by IL-4/IL-13 express IL-2R gamma 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-4R alpha/IL-13R alpha 1 receptors in the keratinocyte. Whilst IL-2R gamma, 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-2R gamma in keratinocytes and its role in alteration of keratinocyte function and epidermal barrier. IL-2R gamma expression in keratinocytes was studied using both reconstructed human epidermis (RHE) exposed to IL-4/IL-13 and AD skin. IL-2R gamma induction by type II receptor has been analyzed using JAK inhibitors and RHE knockout (KO) for IL13RA1. IL-2R gamma function was investigated in RHE KO for IL2RG. In RHE, IL-4/IL-13 induce expression of IL-2R gamma at the mRNA and protein levels. Its mRNA expression is also visualized in keratinocytes of lesional AD skin. IL-2R gamma 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-13R alpha 2 is reported in RHE KO for IL2RG than in not edited RHE. These results demonstrate IL-2R gamma induction in keratinocytes through activation of type II receptor. IL-2R gamma is involved in the alteration of the epidermal barrier and in the regulation of IL-13R alpha 2 expression. Observation of IL-2R gamma expression by keratinocytes inside AD lesional skin suggests a role for this receptor subunit in the disease.