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- W4366171275 abstract "The immune response in atopic dermatitis (AD) is driven predominantly by T helper (Th2) cells. The Th2-type cytokines interleukin (IL)-4, and IL-13 activate the Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway, which is essential for their pro-inflammatory action and detrimental effects on the permeability barrier in the epidermis. The lipid abnormalities driven by Th2-type cytokines have not been completely elucidated in AD. The objective of this study was to investigate the role of JAK/STAT in the lipid perturbations in the 3D-epidermal equivalent model of AD conditioned by Th2-type cytokines. We used the small molecule JAK inhibitor tofacitinib to delineate effects involving the JAK/STAT signaling pathway in the lipid perturbation. Th2-type cytokines caused decrement in the elongation process of fatty acids and in the ceramide synthesis, as demonstrated by the reduced levels of ELOVLs 1, 3, and 6, and SPT mRNAs. In contrast, mRNAs of the lipid metabolism-related enzymes DEGS2 and CA2 were increased. Expression levels of PPARG mRNA were also significantly decreased. Altogether, these effects were abrogated by tofacitinib. Th2 signals caused a significant depletion of triglycerides (TGs) paralleled by a lower content of intracellular lipid droplets and increased levels of phosphatidylcholines (PCs). The depletion of TGs was partly associated with the inhibition of the monounsaturated palmitoleic acid formation. Likely, the observed lipid abnormalities occurred prior to changes in ceramide profiles, which were minimally perturbed. Lipid changes induced by Th2-type cytokines were abrogated upon co-treatment with tofacitinib. In conclusion, inhibition of JAK/STAT activation counteracts the unbalance in the lipid metabolism caused by Th2-type cytokines." @default.
- W4366171275 created "2023-04-19" @default.
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- W4366171275 date "2023-05-01" @default.
- W4366171275 modified "2023-09-28" @default.
- W4366171275 title "789 Inhibition of the JAK/STAT signaling pathway prevents the lipid perturbation induced by Th2-type cytokines in 3D human epidermal equivalents" @default.
- W4366171275 doi "https://doi.org/10.1016/j.jid.2023.03.798" @default.
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