Interferon in Systemic Lupus Erythematosus

但前提是。 系统性红斑狼疮(SLE)是一种由终末器官引起的自身免疫性疾病 以核酸免疫复合体为靶点的自身抗体介导的损伤，以及 炎性细胞及其产物。虽然重要的观察结果与免疫调节和 系统性红斑狼疮的效应机制提示了一些抑制自身抗体的治疗方法 产生和消除组织损伤，在传入阶段进行干预是非常可取的。 系统性红斑狼疮，当自身免疫正在发展的时候。不幸的是，关于这些早期的信息更少。 事件。最近的数据记录了由受调控基因编码的mRNAs的显著过度表达 狼疮患者外周血单核细胞中干扰素的检测鉴于多效性效应 在免疫功能的不同方面，其中许多可能有助于产生 自身免疫和炎症，确定上游触发因素和 导致系统性红斑狼疮I型干扰素(干扰素-a)靶基因激活的细胞内途径。在这方面， 我们的数据表明，在SLE患者中，RNA在激活干扰素途径中具有潜在的作用。建议数 研究将集中于分析导致基因表达增加的触发因素和途径 干扰素-a及其下游靶基因。这项研究将解决这样一种假设，即基因的激活 通过RNA依赖的Toll样受体(TLR)途径表达是干扰素的重要机制 在系统性红斑狼疮中，途径激活和免疫系统激活改变。具体目标是：1)确定 SLE中介导干扰素表达的TLR通路；2)研究SLE中TLR通路激活的刺激因素 3)确定SLE中TLR通路激活的下游靶点；4)研究SLE中TLR通路激活的下游靶点 系统性红斑狼疮淋巴细胞对干扰素的应答对这一重要途径的阐明应该会导致更有针对性的 系统性自身免疫性疾病中疾病介质的调节。

PROVIDED. Systemic lupus erythematosus (SLE) is an autoimmune disease with significant morbidity due to end organ damage mediated by autoantibodies that target nucleic acid-containing immune complexes, along with inflammatory cells and their products. While important observations related to immune regulation and effector mechanisms in SLE have suggested some therapeutic approaches to inhibit autoantibody production and abrogate tissue damage, it would be highly desirable to intervene at the afferent stage of SLE, when autoimmunity is developing. Unfortunately, less information is available regarding these early events. Recent data have documented prominent overexpression of mRNAs encoded by genes regulated by interferons (IFNs) in peripheral blood mononuclear cells from lupus patients. In view of the pleiotropic effects of IFNs on diverse aspects of immune function, many of which could contribute to generation of autoimmunity and inflammation, it would be of high importance to determine the upstream triggers and intracellular pathways that account for activation of the type I IFN (IFN-a) target genes in SLE. In that regard, our data indicate a potential role for RNA in the activation of the IFN pathway in SLE patients. The proposed research will focus on an analysis of the triggers and pathways that account for the increased expression of IFN-a and its downstream target genes. The research will address the hypothesis that activation of gene expression through an RNA-dependent Toll-like receptor (TLR) pathway is an important mechanism of IFN pathway activation, and altered immune system activation, in SLE. The specific aims are: 1) To identify the TLR pathways that mediate IFN expression in SLE; 2) To study the stimuli for TLR pathway activation in SLE; 3) To characterize the downstream targets of TLR pathway activation in SLE; and 4) To study the response of SLE lymphocytes to IFN. Elucidation of this important pathway should lead to more targeted modulation of disease mediators in systemic autoimmune diseases.