The Slamf3, Slamf5, and Slamf6 receptor-induced pathways to murine lupus

Slamf3、Slamf5 和 Slamf6 受体诱导的小鼠狼疮途径

• 批准号: 8513251
• 负责人: CORNELIS P TERHORST
• 金额: $ 110.33万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8513251
• 关键词: Amino Acid Sequence; Autoantibodies; Autoimmunity; B-Lymphocytes; Biological Markers; CD4 Positive T Lymphocytes; Complement; Dendritic Cells; Development; Diagnostic; Disease; Drug Targeting; Engineering; Gene Family; Helper-Inducer T-Lymphocyte; Human; Immune response; Immunosuppressive Agents; Inbred BALB C Mice; Instruction; Lead; Lupus; Monitor; Monoclonal Antibodies; Mouse Strains; Mus; Pathogenesis; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Play; Production; Protein Isoforms; Regulatory Pathway; Research; Research Personnel; Role; Signal Pathway; Signal Transduction; Surface; Systemic Lupus Erythematosus; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Transgenes; Translating; Translations; Treatment Protocols; Variant; Work; congenic; design; in vivo; indexing; innovation; novel; programs; receptor; research study; tool

PROJECT SUMMARY (See instructions): SLAMF receptors and their adapters SAP and EAT-2 play a major role in human and mouse innate and adaptive immune response. Investigators in this Program Project have discovered that in mice several of these receptors either positively or negatively regulate the development of autoimmunity, including lupus related pathology. Excitingly, preliminary studies have revealed deviations in signaling pathways initiated by several SLAMF receptors in immunocytes isolated from patients with systemic lupus erythematosus (SLE). The overall hypothesis of Project #1 is that the mouse receptors Slamf3, 5, and 6 and their isoforms govern immune responses involved in the pathogenesis of murine lupus. The experiments that are designed to test this hypothesis are grouped as follows: Specific Aim#1: Testing the hypothesis that the three Slamf6 receptor isoforms initiate distinct positive and negative regulatory pathways to lupus. Specific Aim #2: Testing the hypothesis that the Slamf5 receptor governs signaling in T and B cells and DC during the pathogenesis of mouse lupus. Specific Aim #3: Testing the hypothesis that Slamf3 receptor initiated signaling controls autoantibody production.

项目摘要（请参阅说明）： SLAMF受体及其适配器SAP和EAT-2在人类和小鼠先天和适应性免疫反应中起着重要作用。该计划项目中的研究人员发现，在小鼠中，其中几个受体对自身免疫性的发展（包括狼疮相关病理学）进行了负调节。令人兴奋的是，初步研究揭示了由来自全身性红斑狼疮患者分离的免疫细胞中的几个SLAMF受体引发的信号传导途径的偏差（SLE）。 项目＃1的总体假设是小鼠受体SLAMF3、5和6及其同工型控制与鼠狼疮发病机理有关的免疫反应。旨在检验该假设的实验分组如下： 特定目的＃1：测试三种SLAMF6受体同工型启动狼疮的阳性和阴性调节途径的假设。 具体目的＃2：检验以下假设：SLAMF5受体在小鼠狼疮的发病机理期间控制T和B细胞和DC的信号传导。 特定目的＃3：测试SLAMF3受体启动信号传导控制自身抗体的假设。