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: 7960363
• 负责人: Jay Reddy
• 金额: $ 11.23万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960363
• 关键词: Arthritis; Autoimmune Diseases; Autoimmune Responses; Autoimmunity; Biology; 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; Oxidation-Reduction; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 即使人类携带自动反应性B和T细胞，自身免疫反应也不会自发发生，并且这些细胞受到教育为自我组织。 自耐受性破坏的机制是理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，导致自身免疫性疾病的损失。中性粒细胞胞质因子1（NCF1，别名P47Phox）的突变导致对关节炎自发发展的敏感性增强，这归因于氧化爆发的降低（1，2），这意味着ROS在控制自身免疫反应中具有有益的作用。 我们的研究将集中于人类自身免疫性疾病多发性硬化症（MS）。 我们将使用用髓磷脂蛋白蛋白（PLP）诱导的鼠实验性自身免疫性脑脊髓炎（EAE）作为人类MS的疾病模型（3）。 拟议的研究将涉及使用EAE敏感，SJL和抗EAE的B10.s菌株的使用。 这是一个有用的框架，用于确定ROS在定义条件下对自身免疫性的遗传抗性中的作用。