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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., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Keratinocyte monolayers, cultured in immersed conditions, constitute a frequently used in vitro model system to study keratinocytes behaviour in response to environmental assaults. However, monolayers lack the keratinocyte terminal differentiation and the organization of the epidermal tissue, which are observed in vivo. Advancements of in vitro techniques were used to reconstruct three-dimensional equivalents that mimic human epidermis in terms of layering, differentiation and barrier function. Here, we update a published method and illustrate the progressive morphogenesis responsible for in vitro reconstruction. The analysis of cell proliferation, expression of differentiation markers and barrier efficacy demonstrate the excellent similarity of the reconstructed tissue with normal human epidermis. Availability of epidermal tissue during its reconstruction phase in culture appears crucial for studies intending to challenge the barrier function., (© 2012 John Wiley & Sons A/S.)