当前位置: X-MOL 学术Immunol. Rev. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Immunometabolism in the development of rheumatoid arthritis.
Immunological Reviews ( IF 8.7 ) Pub Date : 2020-01-27 , DOI: 10.1111/imr.12838
Cornelia M Weyand 1, 2 , Jörg J Goronzy 1, 2
Affiliation  

In rheumatoid arthritis (RA), breakdown of self-tolerance and onset of clinical disease are separated in time and space, supporting a multi-hit model in which emergence of autoreactive T cells is a pinnacle pathogenic event. Determining factors in T cell differentiation and survival include antigen recognition, but also the metabolic machinery that provides energy and biosynthetic molecules for cell building. Studies in patients with RA have yielded a disease-specific metabolic signature, which enables naive CD4 T cells to differentiate into pro-inflammatory helper T cells that are prone to invade into tissue and elicit inflammation through immunogenic cell death. A typifying property of RA CD4 T cells is the shunting of glucose away from glycolytic breakdown and mitochondrial processing toward the pentose phosphate pathway, favoring anabolic over catabolic reactions. Key defects have been localized to the mitochondria and the lysosome; including instability of mitochondrial DNA due to the lack of the DNA repair nuclease MRE11A and inefficient lysosomal tethering of AMPK due to deficiency of N-myristoyltransferase 1 (NMT1). The molecular taxonomy of the metabolically reprogrammed RA T cells includes glycolytic enzymes (glucose-6-phosphate dehydrogenase, phosphofructokinase), DNA repair molecules (MRE11A, ATM), regulators of protein trafficking (NMT1), and the membrane adapter protein TSK5. As the mechanisms determining abnormal T cell behavior in RA are unraveled, opportunities will emerge to interject autoimmune T cells by targeting their metabolic checkpoints.

中文翻译:

类风湿关节炎发展中的免疫代谢。

在类风湿性关节炎 (RA) 中,自我耐受性的崩溃和临床疾病的发作在时间和空间上是分开的,支持多重打击模型,其中自身反应性 T 细胞的出现是最重要的致病事件。T 细胞分化和存活的决定因素包括抗原识别,还包括为细胞构建提供能量和生物合成分子的代谢机制。对 RA 患者的研究产生了疾病特异性代谢特征,使初始 CD4 T 细胞能够分化为促炎辅助 T 细胞,这些细胞易于侵入组织并通过免疫原性细胞死亡引发炎症。RA CD4 T 细胞的一个典型特性是将葡萄糖从糖酵解分解和线粒体加工转向磷酸戊糖途径,有利于合成代谢而不是分解代谢反应。关键缺陷位于线粒体和溶酶体;包括由于缺乏 DNA 修复核酸酶 MRE11A 导致的线粒体 DNA 不稳定,以及由于缺乏 N-肉豆蔻酰转移酶 1 (NMT1) 导致的 AMPK 溶酶体束缚效率低下。代谢重编程的 RA T 细胞的分子分类包括糖酵解酶(6-磷酸葡萄糖脱氢酶、磷酸果糖激酶)、DNA 修复分子(MRE11A、ATM)、蛋白质运输调节因子(NMT1)和膜接头蛋白 TSK5。随着确定 RA 中 T 细胞异常行为的机制被阐明,将出现通过靶向自身免疫 T 细胞的代谢检查点来插入自身免疫 T 细胞的机会。
更新日期:2020-02-27
down
wechat
bug