022 The role of ISG15-USP18 axis in oxidative stress-induced vitiligo

Vitiligo is a relatively common, acquired depigmenting disease caused by the loss of epidermal melanocytes. Oxidative stress known to participate in initiation vitiligo triggering autoimmunity. In this study, we tried identify factors serving as bridge between oxidative and autoimmunity vitiligo. According RNA sequencing analysis on H2O2-treated melanocytes, interferon-stimulated gene 15 (ISG15) among interferon signaling-related genes were particularly upregulated. melanocytes showed significantly higher expression ISG15 compared normal Also, ubiquitin-specific peptidase 18 (USP18), which deconjugates was downregulated USP18 knockout displayed senescence changes upregulation similar Additionally, hypermethylation promoter region observed skin tissues Skin blood patients exhibited elevated expressions ISG15. Finally, extracellular found induce interferon-γ production from peripheral mononuclear cells via LFA-1 receptor. conclusion, increases through hypermethylation, leads immune cells, main pathogenic cytokine The ISG15-USP18 pathway might be important stress-induced pathogenesis.