Department of Dermatology, Yale University School of Medicine, New Haven, Conn.
Department of Dermatology, Yale University School of Medicine, New Haven, Conn.
J Allergy Clin Immunol. 2021 Mar;147(3):814-826. doi: 10.1016/j.jaci.2020.10.022. Epub 2020 Oct 28.
Autoimmune and inflammatory diseases are common and diverse, and they can affect nearly any organ system. Much of the pathogenesis of these diseases is related to dysregulated cytokine activity. Historically, autoimmune and inflammatory diseases have been treated with medications that nonspecifically suppress the immune system. mAbs that block the action of pathogenic cytokines emerged 2 decades ago and have become widely useful. More recently, agents that simultaneously block multiple pathogenic cytokines via inhibition of the downstream Janus kinase (JAK)-signal transducer and activator of transcription pathway have emerged and are becoming increasingly important. These small-molecule inhibitors, collectively termed JAK inhibitors, are US Food and Drug Administration-approved in a few autoimmune/inflammatory disorders and are being evaluated in many others. Here, we review the biology of the JAK-signal transducer and activator of transcription pathway and the use of JAK inhibitors to treat autoimmune and inflammatory diseases across medical subspecialties.
自身免疫和炎症性疾病很常见且种类繁多,它们几乎可以影响任何器官系统。这些疾病的发病机制很大程度上与细胞因子活性失调有关。在历史上,自身免疫和炎症性疾病的治疗药物是非特异性抑制免疫系统的药物。20 年前出现了可以阻断致病细胞因子作用的单克隆抗体(mAb),并得到了广泛应用。最近,通过抑制下游 Janus 激酶(JAK)-信号转导和转录激活因子通路来同时阻断多种致病细胞因子的药物也已出现,并变得越来越重要。这些小分子抑制剂统称为 JAK 抑制剂,已在美国食品和药物管理局(FDA)批准用于少数几种自身免疫/炎症性疾病,并正在许多其他疾病中进行评估。在这里,我们回顾 JAK-信号转导和转录激活因子通路的生物学特性以及 JAK 抑制剂在治疗跨医学亚专科的自身免疫和炎症性疾病中的应用。