ROLE OF REACTIVE OXYGEN SPECIES IN THE GENETIC RESISTANCE TO AUTOIMMUNITY

活性氧在自身免疫遗传抵抗中的作用

• 批准号: 8168309
• 负责人: Jay Reddy
• 金额: $ 14.17万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168309
• 关键词: Arthritis; Autoimmune Diseases; Autoimmune Responses; Autoimmunity; Cells; Computer Retrieval of Information on Scientific Projects Database; Development; Disease model; Encephalomyelitis; Experimental Autoimmune Encephalomyelitis; Funding; Genetic; Grant; Human; Institution; Investigation; Maintenance; Mouse Strains; Multiple Sclerosis; Mus; Mutation; Myelin Proteolipid Protein; Predisposition; Reactive Oxygen Species; Research; Research Personnel; Resistance; Resources; Respiratory Burst; Role; Self Tolerance; Source; T-Lymphocyte; Tissues; United States National Institutes of Health; neutrophil

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autoimmune responses do not occur spontaneously, even though humans carry autoreactive B and T cells, and these cells are educated to be tolerant to self-tissues. The mechanisms by which self tolerance is broken are the keys to the understanding of autoimmune diseases. It has been recently suggested that reactive oxygen species (ROS) are critical for the maintenance of T cell tolerance, the loss of which results in autoimmune diseases. A mutation in neutrophil cytosolic factor 1 (Ncf1, alias p47phox) leads to enhanced susceptibility to the spontaneous development of arthritis, and it is attributed to reduced oxidative burst (1, 2), implying that ROS have a beneficial role in controlling autoimmune responses. Our investigations will focus on multiple sclerosis (MS), an autoimmune disease in humans. We will use murine experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) as the disease model for MS in humans (3). The proposed studies will involve the use of EAE-susceptible, SJL and EAE-resistant B10.S strains of mice. This is a useful framework to determine the role of ROS in the genetic resistance to autoimmunity under defined conditions.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 尽管人类携带自身反应性 B 细胞和 T 细胞，并且这些细胞被训练对自身组织具有耐受性，但自身免疫反应不会自发发生。 自我耐受被破坏的机制是了解自身免疫性疾病的关键。 最近有人提出，活性氧 (ROS) 对于维持 T 细胞耐受性至关重要，T 细胞耐受性的丧失会导致自身免疫性疾病。中性粒细胞胞质因子 1（Ncf1，别名 p47phox）的突变会导致关节炎自发发展的易感性增强，这归因于氧化爆发减少 (1, 2)，这意味着 ROS 在控制自身免疫反应方面具有有益作用。 我们的研究重点是多发性硬化症（MS），一种人类自身免疫性疾病。 我们将使用髓鞘蛋白脂质蛋白 (PLP) 诱导的小鼠实验性自身免疫性脑脊髓炎 (EAE) 作为人类多发性硬化症的疾病模型 (3)。 拟议的研究将涉及使用 EAE 敏感、SJL 和 EAE 抗性 B10.S 品系小鼠。 这是一个有用的框架，可以确定 ROS 在特定条件下对自身免疫的遗传抗性中的作用。