Chronic sleep deprivation promotes experimental autoimmune uveitis through STAT1 phosphorylation, ISG15 expression...

Chronic sleep deprivation (CSD) is increasingly common in modern society and is linked to various diseases, including autoimmune conditions like experimental autoimmune uveitis (EAU), a severe ocular inflammation. The pathogenesis of EAU remains unclear, but poor sleep quality has been shown to exacerbate inflammation through immune modulation. To explore this relationship, we conducted a clinical study at the Ophthalmology Center of Renmin Hospital of Wuhan University (July 2023-July 2024), assessing sleep quality in uveitis patients using the Pittsburgh Sleep Quality Index (PSQI). Based on PSQI scores, patients were categorized into four groups, and their symptoms and characteristics were recorded. Simultaneously, a B10.RIII mouse model of CSD and EAU was developed. Western blotting assessed the phosphorylation of Signal Transducer and Activator of Transcription 1 (STAT1) and the expression of Interferon-Stimulated Gene 15 (ISG15) expression, while immunofluorescence and western blotting evaluated macrophage activity and cytokine secretion. Clinical results showed a strong correlation between poor sleep quality and worsened inflammatory symptoms. In mice, CSD increased STAT1 phosphorylation and ISG15 expression, enhancing macrophage activity and worsening ocular inflammation. Our findings suggest that CSD exacerbates EAU through STAT1 phosphorylation, ISG15 expression, and macrophage activation. The clinical data further support this mechanism, indicating that improving sleep quality could reduce the risk of autoimmune diseases and offering new insights into the connection between sleep and immune function.