Raychaudhuri Smriti K, Raychaudhuri Siba P
aVA Medical Center, Sacramento, California bDivision of Rheumatology, Allergy and Clinical immunology, University of California School of Medicine, Davis, California, USA.
Curr Opin Rheumatol. 2017 Jul;29(4):311-316. doi: 10.1097/BOR.0000000000000399.
Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway represents a group of several intracellular molecules with a key role in signal pathways activated by growth factors and cytokines. These kinase proteins are associated with the signaling process of multiple key cytokines, which regulates various T-cell subpopulations and their effector cytokines. Development of novel drugs to inhibit this kinase cascade is an emerging field in clinical immunology. Thus, it is essential to have insights about the regulatory role of the JAK-STAT cytokine signaling in relation to autoimmune diseases and its applications in spondyloarthritis.
JAK-STAT kinase signaling proteins have been extensively studied in rheumatoid arthritis. Initial observations suggest that JAK-STAT kinase signaling cascade regulates activation and proliferation of the IL17 effector memory T cells and thus has a potential role in the pathogenesis of psoriasis, psoriatic arthritis and ankylosing spondylitis.
Here, we provide an overview of the clinical rheumatologists about the significance of JAK-STAT signaling system in rheumatic diseases and introduce the potential application of JAK and STAT inhibitors in spondyloarthritis.
细胞因子是自身免疫的主要驱动因素,靶向细胞因子的生物制剂彻底改变了免疫介导疾病的治疗。Janus激酶/信号转导子和转录激活子(JAK-STAT)通路代表了一组在生长因子和细胞因子激活的信号通路中起关键作用的细胞内分子。这些激酶蛋白与多种关键细胞因子的信号传导过程相关,调节各种T细胞亚群及其效应细胞因子。开发抑制这种激酶级联反应的新型药物是临床免疫学中一个新兴的领域。因此,了解JAK-STAT细胞因子信号在自身免疫性疾病中的调节作用及其在脊柱关节炎中的应用至关重要。
JAK-STAT激酶信号蛋白在类风湿关节炎中已得到广泛研究。初步观察表明,JAK-STAT激酶信号级联调节IL17效应记忆T细胞的激活和增殖,因此在银屑病、银屑病关节炎和强直性脊柱炎的发病机制中具有潜在作用。
在此,我们向临床风湿病学家概述JAK-STAT信号系统在风湿性疾病中的重要性,并介绍JAK和STAT抑制剂在脊柱关节炎中的潜在应用。