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- W4366172105 abstract "Atopic dermatitis (AD) is an inflammatory disease characterized by alteration of the epidermal barrier that results from local Th2 immune response. Interleukin (IL)-4 and IL-13 are Th2 cytokines playing major roles in alterations of the epidermal barrier through activation of the IL-4Rα/IL-13Rα1 type II receptor constitutively expressed on keratinocytes. Whereas the type I receptor IL-4Rα/IL-2Rγ is thought restricted to hematopoietic cell types, our recent data reported expression of IL-2Rγ receptor subunit by keratinocytes in reconstructed human epidermis exposed to IL-4 and IL-13, suggesting eventual formation of type I receptors on this cell type if embedded in 3D-epidermis. Indeed, no expression of IL-2Rγ can be observed in keratinocytes, either proliferating or differentiating, when this cell type is cultured as a monolayer.In vivo, IL-2Rγ expression by epidermal keratinocytes happens in lesional AD skin. Since both type I and type II receptors activate JAK/STAT signaling, downstream pathways were inhibited using a STAT6 inhibitor (AS1517499), or using four different JAK inhibitors (JAKi), namely tofacitinib, upadacitinib, ruxolitinib and deucravacitinib. In keratinocytes exposed to IL-4 or IL-13, each inhibitor prevents or decreases STAT6 phosphorylation. All JAKi inhibit Th2-induced IL-2Rγ expression by keratinocytes, whereas AS1517499 partially impedes this induction. Together, these results indicate that IL-2Rγ expression in keratinocytes does not solely rely on STAT6 activation and suggest a role for enhanced phosphorylation of STAT3 in the Th2-induced IL-2Rγ expression. In conclusion, IL-2Rγ expression by keratinocytes after STAT6 and STAT3 activation must be taken into consideration for a comprehensive understanding of actors and mechanisms targeted by current AD treatments like blocking antibodies, or JAKi." @default.
- W4366172105 created "2023-04-19" @default.
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- W4366172105 date "2023-05-01" @default.
- W4366172105 modified "2023-09-28" @default.
- W4366172105 title "720 Expression of IL-2Rγ receptor subunit by human keratinocytes in epidermis is induced through STAT6 and STAT3 activation by IL-4 and IL-13" @default.
- W4366172105 doi "https://doi.org/10.1016/j.jid.2023.03.729" @default.
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