ROLE OF REACTIVE OXYGEN SPECIES IN THE GENETIC RESISTANCE TO AUTOIMMUNITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 即使人类携带自体反应性B和T细胞，自身免疫反应也不会自发发生，这些细胞被培养成对自身组织具有耐受性。自我耐受性被打破的机制是理解自身免疫性疾病的关键。最近有研究表明，活性氧簇(ROS)在维持T细胞耐受中起着至关重要的作用，失去ROS会导致自身免疫性疾病。中性粒细胞胞浆因子1(Ncf1，别名p47Phox)的突变导致关节炎自发发展的易感性增加，这归因于氧化猝发(1，2)的减少，这意味着ROS在控制自身免疫反应方面具有有益的作用。我们的研究将集中在多发性硬化症(MS)上，这是人类的一种自身免疫性疾病。我们将使用髓磷脂蛋白(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。拟议的研究将涉及使用对EAE敏感的、SJL和抗EAE的B10.S小鼠品系。这是一个有用的框架来确定ROS在特定条件下对自身免疫的遗传抵抗中的作用。

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.