789 Inhibition of the JAK/STAT signaling pathway prevents the lipid perturbation induced by Th2-type cytokines in 3D human epidermal equivalents

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