Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases

被引：569

作者：

Schwartz, Daniella M. ^{[1
,2
]}

Bonelli, Michael ^{[3
]}

Gadina, Massimo ^{[1
,2
]}

O'Shea, John J. ^{[1
,2
]}

机构：

[1] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA

[2] NIAMSD, Translat Immunol Sect, NIH, Bethesda, MD 20892 USA

[3] Med Univ Vienna, Dept Rheumatol, A-1090 Vienna, Austria

来源：

NATURE REVIEWS RHEUMATOLOGY | 2016年 / 12卷 / 01期

关键词：

D O I：

10.1038/nrrheum.2015.167

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Despite the effectiveness of these drugs, they do not induce complete remission in all patients, prompting the development of alternative strategies - including targeting of intracellular signal transduction pathways downstream of cytokines. Many cytokines that bind type I and type II cytokine receptors are critical regulators of immune-mediated diseases and employ the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway to exert their effect. Pharmacological inhibition of JAKs blocks the actions of type I/II cytokines, and within the past 3 years therapeutic JAK inhibitors, or Jakinibs, have become available to rheumatologists. Jakinibs have proven effective for the treatment of rheumatoid arthritis and other inflammatory diseases. Adverse effects of these agents are largely related to their mode of action and include infections and hyperlipidemia. Jakinibs are currently being investigated for a number of new indications, and second-generation selective Jakinibs are being developed and tested. Targeting STATs could be a future avenue for the treatment of rheumatologic diseases, although substantial challenges remain. Nonetheless, the ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease.

引用

页码：25 / 36

页数：12

共 123 条

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