347 Chronic Inflammation of Keratinocytes Leads to Autophagy Impairment in Psoriasis

Psoriasis is an inflammatory disorder which leads to the improper stratification of epidermal keratinocytes. Autophagic flux analysis our established cell lines has shown that autophagy functionally active in healthy keratinocytes but impaired psoriatic To mirror psoriasis vitro we custom-made a cytokine cocktail induced IL-1β release keratinocyte cultures. Stimulation by this chronic similarly causes block and accumulation key proteins. Interestingly, stimulus LC3-I accumulation, rather than LC3-II, suggesting inflammation blocks prior final stages autophagosome autolysosome formation. In addition, p62 upregulation indicates disruption cargo degradation via lysosomal compartment. Increased ATG4, ATG7 ATG12 expression these were not cause pathway. Changes phospholipid metabolism been reported skin conditions including Phosphatidylethanolamine (PE) downregulation PE essential for conversion LC3-II. By inducing production inflamed keratinocytes, show restoration pathway functionality. Transcriptomic data identified several autophagic genes with significantly deregulated samples (n=398) compared matched or non-matched (n=587) controls. Immunofluorescence staining human confirmed differences marker deregulation membrane We have impairs downregulating altering compartment integrity. Our supports stimulation as beneficial approach counteract such psoriasis.