Augmentation of PRDX1–DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation

作者：Wenzhen Dang, Xiaomin Wang, Hongbo Li, Yixuan Xu, Xinyu Li, Siqi Huang, Hongru Tao, Xiao Li, Yulin Yang, Lijiang Xuan, Wei‐Lie Xiao, De‐an Guo, Hao Zhang, Qiong Wu, Jie Zheng, Xiaoyan Shen, Kaixian Chen, Heng Xu, Yuanyuan Zhang, Cheng Luo · 发表于：Acta Pharmaceutica Sinica B · 年份：2025 · DOI：10.1016/j.apsb.2025.06.006 · 被引用次数：4 · 研究领域：Heat shock proteins research、Signaling Pathways in Disease、interferon and immune responses

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.