فهرست نشریات علمی دسترسی آزاد ایران

Background: Bullous pemphigoid (BP) is a chronic autoimmune blistering disease characterized by subepidermal inflammation and the presence of autoantibodies against hemidesmosomal proteins. Corticosteroids remain the primary treatment; however, their longterm toxicity and incomplete disease control highlight the need for targeted therapies. Tofacitinib, a Janus kinase (JAK) inhibitor, has demonstrated efficacy in treating inflammatory skin disorders, but its molecular effects in BP are not yet well understood.Methods: We performed an integrative transcriptomic analysis to investigate tofacitinib-induced gene expression changes in BP compared with psoriasis and rheumatoid arthritis. Differential expression and weighted gene co-expression network analyses were applied to identify disease-associated modules and assess transcriptional regulation mediated by tofacitinib. Functional enrichment analysis was conducted to characterize biological pathways, and drug repositioning analysis was performed to compare tofacitinib-induced profiles with those of glucocorticoid-associated compounds.Results: Modules enriched in interleukin signaling, neutrophil degranulation, and cytokine-mediated pathways were identified across diseases. Tofacitinib consistently downregulated key inflammatory mediators, including STAT1, STAT3, and IL-6, indicating potent suppression of the JAK–STAT axis. Drug repositioning analysis revealed overlap between tofacitinib and glucocorticoid-associated compounds, notably triamcinolone acetonide, highlighting shared immunosuppressive signatures while suggesting distinct mechanistic effects.Conclusion: This study provides the first transcriptomic insights into tofacitinib activity in BP, demonstrating suppression of the JAK–STAT pathway and potential synergy with NF-κB inhibition. These findings suggest new avenues for rational drug repurposing and combination therapy in autoimmune blistering diseases. Further experimental validation is necessary to confirm these molecular interactions and their implications for precision treatment in BP.