JAK1/2 Inhibitors Alleviate the Damage of Intercellular Adhesion by Reducing Endoplasmic Reticulum Stress‐Induced Apoptosis in Pemphigus Vulgaris

ABSTRACT Pemphigus vulgaris (PV), a severe autoimmune disease with high morbidity and mortality, necessitates innovative therapies to improve outcomes while minimising the adverse effects of conventional immunosuppressants. Immunohistochemical analysis revealed elevated phosphorylated Janus kinase (p‐JAK)1 and p‐JAK2 expression in PV lesions, complemented by transcriptome data showing JAK/STAT pathway dysregulation. Using a PV acantholysis model, we demonstrated that Ruxolitinib, a JAK1/2 inhibitor, significantly reduced keratinocyte apoptosis, enhanced cell adhesion, and alleviated endoplasmic reticulum (ER) stress. Additionally, Ruxolitinib mitigated tunicamycin‐induced ER stress and apoptosis in HaCaT cells. These findings establish a crucial role for JAK1/2 in PV pathogenesis, demonstrating that their inhibition alleviates ER stress, reduces apoptosis, and improves cell adhesion. Our results provide a theoretical foundation for the clinical application of JAK inhibitors in PV treatment.