Division of Rheumatology, Department of Medicine, College of Medicine, State University of New York Upstate Medical University, Syracuse, New York, USA.
Department of Microbiology and Immunology, College of Medicine, State University of New York Upstate Medical University, Syracuse, New York, USA.
Antioxid Redox Signal. 2022 Mar;36(7-9):367-388. doi: 10.1089/ars.2021.0068. Epub 2021 Jul 7.
Systemic autoimmunity affects 3%-5% of the population worldwide. Systemic lupus erythematosus (SLE) is a prototypical form of such condition, which affects 20-150 of 100,000 people globally. Liver dysfunction, defined by increased immune cell infiltration into the hepatic parenchyma, is an understudied manifestation that affects up to 20% of SLE patients. Autoimmunity in SLE involves proinflammatory lineage specification in the immune system that occurs with oxidative stress and profound changes in cellular metabolism. As the primary metabolic organ of the body, the liver is uniquely capable to encounter oxidative stress through first-pass derivatization and filtering of waste products. The traffic of immune cells from their development through recirculation in the liver is guided by cell adhesion molecules (CAMs) and integrins, cell surface proteins that tightly anchor cells together. The surface expression of CAMs and integrins is regulated endocytic traffic that is sensitive to oxidative stress. Reactive oxygen species (ROS) that elicit oxidative stress in the liver may originate from the mitochondria, the cytosol, or the cell membrane. While hepatic ROS production is a source of vulnerability, it also modulates the development and function of the immune system. In turn, the liver employs antioxidant defense mechanisms to protect itself from damage that can be harnessed to serve as therapeutic mechanisms against autoimmunity, inflammation, and development of hepatocellular carcinoma. This review is aimed at delineating redox control of integrin signaling in the liver and checkpoints of regulatory impact that can be targeted for treatment of inflammation in systemic autoimmunity. . 36, 367-388.
系统性自身免疫影响全球 3%-5%的人口。系统性红斑狼疮 (SLE) 是这种疾病的典型形式，影响全球每 10 万人中有 20-150 人。肝脏功能障碍，定义为免疫细胞浸润肝实质增加，是一种研究不足的表现，影响高达 20%的 SLE 患者。SLE 中的自身免疫涉及免疫系统中促炎谱系的特异性，这是与氧化应激和细胞代谢的深刻变化有关的。作为身体的主要代谢器官，肝脏通过对废物的首过衍生化和过滤，具有独特的应对氧化应激的能力。免疫细胞从其发育到在肝脏中的再循环的运输，是由细胞粘附分子 (CAM) 和整合素引导的，这些是紧密锚定细胞的细胞表面蛋白。CAM 和整合素的表面表达受内吞运输调节，而内吞运输对氧化应激敏感。在肝脏中引起氧化应激的活性氧 (ROS) 可能来自线粒体、细胞质或细胞膜。虽然肝 ROS 产生是易损性的来源，但它也调节免疫系统的发育和功能。反过来，肝脏利用抗氧化防御机制来保护自身免受可能被利用来作为针对自身免疫、炎症和肝细胞癌发展的治疗机制的损伤。这篇综述旨在描绘肝脏中整合素信号的氧化还原控制，以及可以作为治疗系统性自身免疫中炎症的靶点的调节影响的检查点。Nat Rev Immunol. 2023 年 4 月；23(4):225-239. doi: 10.1038/s41577-023-00841-5. Epub 2023 Mar 20. PMID: 36763664.
