Janus激酶抑制剂治疗系统性红斑狼疮的研究进展

Janus kinase⁃inhibitors in the treatment of systemic lupus erythematosus

系统性红斑狼疮(SLE)的发生涉及固有免疫和获得性免疫系统的免疫细胞和细胞因子数量和功能异常。细胞因子介导的异常免疫反应通过共同的Janus激酶/信号传导及转录激活因子(JAK/STAT)信号通路,使JAK/STAT通路成为重要的治疗新靶点。JAK抑制剂可调控JAK/STAT信号通路,抑制免疫细胞的异常激活和引发的炎症反应,已被批准用于治疗类风湿关节炎、银屑病等自身免疫性疾病。动物及临床试验显示,JAK抑制剂治疗SLE和狼疮性肾炎可能具有巨大潜力。本文系统综述了JAK/STAT通路在SLE发病中的作用、JAK抑制剂治疗SLE和狼疮性肾炎的作用机制及临床应用。

The pathogenesis of systemic lupus erythematosus(SLE)involves quantity and function abnormalities of cells and cytokines in both the innate and the acquired immune systems.The cytokine⁃mediated abnormal immune response has a common Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway,making the JAK/STAT path represent an important therapeutic target for SLE.JAK inhibitors,having been approved for rheumatoid arthritis and psoriasis,can inhibit the activation of immune cells and inflammation by regulating JAK/STAT signaling pathways.Animal models and clinical trials have shown the considerable potential of JAK inhibitors in treating SLE and lupus nephritis.This article reviews the role of JAK/STAT pathway in development of SLE,the mechanisms and clinical application of JAK inhibitors in treatment of SLE and lupus nephritis.