类风湿性关节炎
II型胶原
免疫学
关节炎
医学
细胞生物学
化学
生物
作者
Wenxiang Hong,Hongbo Ma,Zhaoxu Yang,Jiaying Wang,Bowen Peng,Longling Wang,Yiwen Du,Lijun Yang,Lijiang Zhang,Zhibin Li,Han Huang,Difeng Zhu,Bo Yang,Qiaojun He,Jiajia Wang,Qinjie Weng,Jiajia Wang,Qinjie Weng
标识
DOI:10.1016/j.apsb.2025.02.004
摘要
Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.
科研通智能强力驱动
Strongly Powered by AbleSci AI