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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 自身免疫反应不会自发发生，即使人类携带自身反应性B和T细胞，并且这些细胞被训练成对自身组织具有耐受性。 自身耐受性被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）是维持T细胞耐受性的关键，其丧失导致自身免疫性疾病。中性粒细胞胞质因子1（Ncf 1，别名p47 phox）的突变导致对关节炎自发发展的易感性增强，并且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中具有有益作用。 我们的研究将集中在多发性硬化症（MS），一种人类自身免疫性疾病。 我们将使用髓磷脂蛋白脂质蛋白（PLP）诱导的小鼠实验性自身免疫性脑脊髓炎（EAE）作为人类MS的疾病模型（3）。 拟定研究将涉及使用EAE敏感、SJL和EAE耐药B10.S小鼠品系。 这是一个有用的框架，以确定在确定的条件下，活性氧在自身免疫的遗传抗性的作用。

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.