179 Oxidative Damage is a Hallmark of Atopic Dermatitis in Humans and Mice

Atopic Dermatitis (AD) is the most common inflammatory skin disease and characterized by a deficient epidermal barrier inflammation. Genetic studies suggest key role of keratinocytes in AD pathogenesis, but alterations proteome that occur full epidermis have not been defined. We performed quantitative proteomics from healthy volunteers lesional non-lesional patient validated results targeted immunofluorescence staining. A large number proteins were identified are differentially abundant vs or skin. They reflect strong inflammation defect keratinocyte differentiation stratification already characterizes Most importantly, they reveal impaired activation NRF2-antioxidant pathway reduced abundance mitochondrial involved metabolic pathways affected epidermis. Functional vitro demonstrate NRF2 abnormalities partially interlinked. In parallel, we characterizing previously established mouse model resembles phenotype. These mice carry keratinocyte-specific knockout for fibroblast growth factor receptor 1 2 genes exhibit several hallmarks AD. showed combined loss these receptors promotes DNA damage senescence vivo. Both features aggravated additional Nrf2, suggesting oxidative stress Together, identify potential an Nrf2-mediated response chronic inflammation, which could be therapeutically explored patients.