Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Linkou, Taoyuan 33305, Taiwan.
Cells. 2020 Nov 12;9(11):2466. doi: 10.3390/cells9112466.
The c-Jun-N-terminal kinase (JNK) is a critical mediator involved in various physiological processes, such as immune responses, and the pathogenesis of various diseases, including autoimmune disorders. JNK is one of the crucial downstream signaling molecules of various immune triggers, mainly proinflammatory cytokines, in autoimmune arthritic conditions, mainly including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. The activation of JNK is regulated in a complex manner by upstream kinases and phosphatases. Noticeably, different subtypes of JNKs behave differentially in immune responses. Furthermore, aside from biologics targeting proinflammatory cytokines, small-molecule inhibitors targeting signaling molecules such as Janus kinases can act as very powerful therapeutics in autoimmune arthritis patients unresponsiveness to conventional synthetic antirheumatic drugs. Nevertheless, despite these encouraging therapies, a population of patients with an inadequate therapeutic response to all currently available medications still remains. These findings identify the critical signaling molecule JNK as an attractive target for investigation of the immunopathogenesis of autoimmune disorders and for consideration as a potential therapeutic target for patients with autoimmune arthritis to achieve better disease control. This review provides a useful overview of the roles of JNK, how JNK is regulated in immunopathogenic responses, and the potential of therapeutically targeting JNK in patients with autoimmune arthritis.
c-Jun-N 末端激酶（JNK）是一种关键的介质，参与各种生理过程，如免疫反应，以及各种疾病的发病机制，包括自身免疫性疾病。JNK 是各种免疫触发物（主要是促炎细胞因子）在自身免疫性关节炎疾病（主要包括类风湿关节炎、强直性脊柱炎和银屑病关节炎）中的关键下游信号分子之一。JNK 的激活受到上游激酶和磷酸酶的复杂调节。值得注意的是，不同亚型的 JNK 在免疫反应中表现出不同的行为。此外，除了针对促炎细胞因子的生物制剂外，针对信号分子（如 Janus 激酶）的小分子抑制剂也可以作为自身免疫性关节炎患者对常规合成抗风湿药物无反应的非常有效的治疗药物。然而，尽管有这些令人鼓舞的治疗方法，仍有一部分患者对所有现有药物的治疗反应不足。这些发现将关键信号分子 JNK 确定为自身免疫性疾病免疫发病机制研究的有吸引力的靶点，并考虑将其作为自身免疫性关节炎患者的潜在治疗靶点，以实现更好的疾病控制。这篇综述提供了 JNK 的作用、JNK 如何在免疫发病机制中调节以及在自身免疫性关节炎患者中靶向 JNK 的潜在治疗作用的有用概述。
