JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects.
JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects.
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JAK-STAT信号作为炎症和自身免疫性疾病的靶标:当前和未来展望
DOI：
10.1007/s40265-017-0701-9
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发表时间：
2017-04
期刊：
影响因子：
11.5
通讯作者：
Schwartz DM
中科院分区：
文献类型：
--
作者：
Banerjee S;Biehl A;Gadina M;Hasni S;Schwartz DM
JAK-STAT信号通路参与类风湿关节炎、银屑病和炎症性肠病等炎症性和自身免疫性疾病的发病机制。许多参与自身免疫性和炎症性疾病发病机制的细胞因子使用JAKs和STATs来转导细胞内信号。JAK和STAT基因的突变会导致许多免疫缺陷综合征，而这些基因的多态与自身免疫性疾病有关。小分子JAK抑制剂(Jakinibs)在风湿病治疗中的成功表明，细胞内信号通路可以作为治疗自身免疫的靶点。托法替尼是第一个风湿性雅奇尼，是美国食品和药物管理局(FDA)批准用于类风湿性关节炎的药物，目前正在接受其他自身免疫性疾病的调查。许多其他Jakinib正处于临床前开发或临床试验的不同阶段。这篇综述描述了JAK-STAT通路，概述了它在自身免疫中的作用，并解释了以JAK-STAT信号为靶点的理论基础/临床前证据。回顾了Jakinibs的安全性和临床疗效，从FDA批准的Jakinib tofacitinib开始，继续到下一代Jakinibs。重点介绍了最近和正在进行的研究，重点是JAK抑制的新指征和JAK-STAT信号阻断的新机制。
The Janus kinase/signal transduction and activator of transcription (JAK–STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases. The success of small-molecule JAK inhibitors (Jakinibs) in the treatment of rheumatologic disease demonstrates that intracellular signaling pathways can be targeted therapeutically to treat autoimmunity. Tofacitinib, the first rheumatologic Jakinib, is US Food and Drug Administration (FDA) approved for rheumatoid arthritis and is currently under investigation for other autoimmune diseases. Many other Jakinibs are in preclinical development or in various phases of clinical trials. This review describes the JAK–STAT pathway, outlines its role in autoimmunity, and explains the rationale/pre-clinical evidence for targeting JAK–STAT signaling. The safety and clinical efficacy of the Jakinibs are reviewed, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation Jakinibs. Recent and ongoing studies are emphasized, with a focus on emerging indications for JAK inhibition and novel mechanisms of JAK–STAT signaling blockade.
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影响因子：
27.4
作者：
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作者：
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通讯作者：
Mebus, Charles
影响因子：
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作者：
Changelian, PS;Flanagan, ME;Borie, DC
通讯作者：
Borie, DC