127 IL-17 acts as the master regulator for metabolic rewiring in skin inflammation and drives keratinocytes towards a hyperproliferative phenotype

Immune system, especially T cells, and their cytokines play a vital role in the progression maintenance of skin inflammation many disorders. Increased frequency IL-17 producing Th17 cells are known to be present lesions psoriasis atopic dermatitis patients. However, roles mechanisms metabolic reprogramming human remain unexplored. Here, we employed multi-omics system biology approach examine mediated alterations primary keratinocytes (HPKs). 1H NMR metabolomics data revealed dysregulation metabolites (glucose malate) involved carbohydrate metabolism. Moreover, lipidomics study increased levels sphingolipid intracellular neutral lipids stimulated HPKs. System using MitoCore model confirmed our findings that upregulated three major pathways: glycolysis, glutaminolysis, lipid synthesis (p-value < 0.05); all resulted cumulative increase nutrient pool for Finally, stable isotope resolved (using U-13C glucose glutamine) biochemical assays validated rewiring central Functionally, modulated redox status Reactive Oxygen Species (ROS) 0.01) inside which turn triggered signaling cascade perturbations rendered towards more proliferative phenotype. Overall, this highlights first time, modulating regulation homeostasis drives hyperproliferation. Our presents novel immuno-metabolism cross-talk extracellular microenvironment affects its pathogenesis.