Role of ISG15 in the Pathogenesis of SLE

ISG15 在 SLE 发病机制中的作用

• 批准号: 7680339
• 负责人: Deborah J Lenschow
• 金额: $ 9.18万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7680339
• 关键词: Autoantibodies; Class; Development; Doctor of Medicine; Doctor of Philosophy; Feasibility Studies; Funding; Immune response; Injury; Interferon Type I; Interferons; Mediating; Modeling; Mus; Nuclear Antigens; Pathogenesis; Play; Reagent; Role; Systemic Lupus Erythematosus; Title; body system; cell type; chronic autoimmune disease; cytokine

Funded RDCC Pilot and Feasibility Study #1 Title: Role of ISG15 in the pathogenesis of SLE PI: Deborah J. Lenschow, M.D., Ph.D. A. Specific Aims: Systemic lupus erythematosis (SLE) is a chronic autoimmune disease characterized by the loss of tolerance to nuclear antigens and the development of pathogenic autoantibodies, resulting in injury to multiple organ systems. Recent studies have implicated type I interferons (IFNs) in the pathogenesis of SLE; however, the downstream IFN effector molecules that mediate these actions are poorly understood. We proposed the following aims to evaluate the role of a recently identified and characterized IFN induced molecule, ISG15, in the pathogenesis of SLE. Aim 1. Determine if ISG15 functions as a cytokine to regulate immune responses. Aim 2. Determine if ISG15 plays a role in the pathogenesis of SLE. During the course of these studies it became apparent that while IFNs are known to play a role in the pathogenesis of SLE in various murine models, little is known about the cell type specific effects of this class of cytokines in these models. We have obtained or are developing reagents for other projects in the lab that will allow us to evaluate cell type specific effects of type I IFNs. We propose to utilize these reagents to pursue this question in murine models of SLE. Aim 3. Determine the cell type specific effects of Type I IFNs in the pathogenesis of SLE.

资助的RDCC飞行员和可行性研究＃1 标题：ISG15在SLE发病机理中的作用 PI：Deborah J. Lenschow，医学博士，博士 A.具体目的： 全身性红斑狼疮（SLE）是一种慢性自身免疫性疾病，其特征是丧失 对核抗原的耐受性和致病性自身抗体的发展，导致损伤 多器官系统。最近的研究已牵涉到发病机理中的I型干扰素（IFN） sle;但是，介导这些作用的下游IFN效应分子很差 理解。我们提出了以下旨在评估最近确定的作用的目的 在SLE的发病机理中表征了IFN诱导的分子ISG15。 AIM 1。确定ISG15是否功能作为调节免疫反应的细胞因子。 AIM 2。确定ISG15是否在SLE的发病机理中起作用。 在这些研究过程中 SLE在各种鼠模型中的发病机理，对细胞类型的特异性效应知之甚少 这些模型中的这类细胞因子。我们已经获得或正在开发其他试剂 实验室的项目将使我们能够评估I型IFN的细胞类型特定效果。我们建议 利用这些试剂在SLE的鼠模型中提出这个问题。 AIM 3。确定I型IFN在SLE发病机理中的细胞类型特异性效应。