Glucose transporter 1 in rheumatoid arthritis and autoimmunity.

IF 7.9 Q1 Medicine Wiley Interdisciplinary Reviews-Systems Biology and Medicine Pub Date : 2020-07-01 Epub Date: 2020-02-21 DOI:10.1002/wsbm.1483
Ekaterina Zezina, Oezen Sercan-Alp, Matthias Herrmann, Nadine Biesemann
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引用次数: 22

Abstract

Knowledge about metabolism of immune cells increased almost exponentially during the last two decades and thereby created the new area immunometabolism. Increased glucose uptake and glycolysis were identified as one of the major drivers in immune cells for rapid adaptation to changes in the microenvironment or external stimuli. These metabolic switches are crucial to generate macromolecules for immune cell proliferation and activation. Glucose transporter 1 (GLUT1), a ubiquitously expressed glucose transporter, is strongly upregulated after innate and adaptive immune cell activation. Deletion or inhibition of GLUT1 blocked T cell proliferation and effector function, antibody production from B cells and reduced inflammatory responses in macrophages. Increased glucose uptake and GLUT1 expression are not only observed in proinflammatory conditions, but also in murine models of autoimmunity as well as in human patients. Rheumatoid arthritis (RA), the most common autoimmune disease, is characterized by infiltration of immune cells, hyperproliferation of fibroblast-like synoviocytes, and destruction of cartilage and bone. These processes create a hypoxic microenvironment in the synovium. Moreover, synovial samples including fibroblast-like synoviocytes from RA patients showed increased lactate level and upregulate GLUT1. Similar upregulation of GLUT1 is observed in systemic lupus erythematosus and psoriasis patients as well as in murine autoimmune models. Inhibition of GLUT1 using either T cell specific knockouts or small molecule GLUT1/glycolysis inhibitors improved phenotypes of different murine autoimmune disease models like arthritis, lupus, and psoriasis. Thereby the therapeutic potential of immunometabolism and especially interference with glycolysis was proven. This article is categorized under: Biological Mechanisms > Metabolism Translational, Genomic, and Systems Medicine > Translational Medicine Physiology > Mammalian Physiology in Health and Disease.

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类风湿性关节炎和自身免疫中的葡萄糖转运蛋白1。
在过去的二十年中,关于免疫细胞代谢的知识几乎呈指数级增长,从而创造了新的领域免疫代谢。葡萄糖摄取增加和糖酵解被认为是免疫细胞快速适应微环境或外部刺激变化的主要驱动因素之一。这些代谢开关对于产生免疫细胞增殖和激活的大分子至关重要。葡萄糖转运蛋白1 (GLUT1)是一种普遍表达的葡萄糖转运蛋白,在先天和适应性免疫细胞激活后被强烈上调。缺失或抑制GLUT1阻断T细胞增殖和效应功能,抑制B细胞产生抗体,减少巨噬细胞的炎症反应。葡萄糖摄取和GLUT1表达的增加不仅在促炎条件下观察到,而且在自身免疫小鼠模型和人类患者中也观察到。类风湿性关节炎(RA)是最常见的自身免疫性疾病,其特征是免疫细胞浸润,成纤维细胞样滑膜细胞过度增生,软骨和骨骼破坏。这些过程在滑膜中产生缺氧微环境。此外,RA患者的滑膜样本(包括成纤维细胞样滑膜细胞)显示乳酸水平升高,GLUT1上调。在系统性红斑狼疮和牛皮癣患者以及小鼠自身免疫模型中也观察到类似的GLUT1上调。使用T细胞特异性敲除或小分子GLUT1/糖酵解抑制剂抑制GLUT1可改善不同小鼠自身免疫性疾病模型(如关节炎、狼疮和牛皮癣)的表型。从而证明了免疫代谢特别是干扰糖酵解的治疗潜力。本文分类如下:生物学机制>代谢、转化、基因组和系统医学>转化医学生理学>健康与疾病中的哺乳动物生理学。
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来源期刊
CiteScore
18.40
自引率
0.00%
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0
审稿时长
>12 weeks
期刊介绍: Journal Name:Wiley Interdisciplinary Reviews-Systems Biology and Medicine Focus: Strong interdisciplinary focus Serves as an encyclopedic reference for systems biology research Conceptual Framework: Systems biology asserts the study of organisms as hierarchical systems or networks Individual biological components interact in complex ways within these systems Article Coverage: Discusses biology, methods, and models Spans systems from a few molecules to whole species Topical Coverage: Developmental Biology Physiology Biological Mechanisms Models of Systems, Properties, and Processes Laboratory Methods and Technologies Translational, Genomic, and Systems Medicine
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