Role of ISG15 in the Pathogenesis of SLE

资助RDCC试点和可行性研究#1 ISG 15在SLE发病机制中的作用 PI：Deborah J. Lenschow，医学博士，博士 A.具体目标： 系统性狼疮性肾炎（SLE）是一种慢性自身免疫性疾病，其特征在于 对核抗原的耐受性和致病性自身抗体的产生，导致对 多器官系统最近的研究表明I型干扰素（IFN）参与了发病机制 然而，介导这些作用的下游IFN效应分子在SLE中的表达很差。 明白我们提出了以下目标，以评估最近确定的 IFN诱导分子ISG 15在SLE发病机制中的作用 目标1.确定ISG 15是否作为细胞因子调节免疫反应。 目标2.确定ISG 15是否在SLE的发病机制中发挥作用。 在这些研究的过程中，很明显，虽然已知IFN在细胞凋亡中起作用，但IFN-γ在细胞凋亡中起作用。 虽然在各种小鼠模型中SLE的发病机制，但关于SLE的细胞类型特异性作用知之甚少。 这类细胞因子在这些模型中。我们已经获得或正在开发其他试剂 在实验室的项目，这将使我们能够评估细胞类型的具体影响I型干扰素。我们建议 利用这些试剂在SLE的小鼠模型中研究这个问题。 目标3.确定I型IFN在SLE发病机制中的细胞类型特异性作用。

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.