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: 9109553
• 负责人: CORNELIS P TERHORST
• 金额: $ 35.1万
• 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 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9109553
• 关键词: Amino Acid Sequence; Autoantibodies; Autoimmunity; B-Lymphocytes; CD4 Positive T Lymphocytes; Complement; Dendritic Cells; Development; Diagnostic; Disease; 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; adaptive immunity; congenic; design; in vivo; indexing; innovation; new therapeutic target; novel; programs; receptor; research study; specific biomarkers; 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.

项目总结（见说明）： SLAMF受体及其衔接子SAP和EAT-2在人类和小鼠先天性和适应性免疫应答中起主要作用。该计划项目的研究人员发现，在小鼠中，这些受体中的几种正或负调节自身免疫的发展，包括狼疮相关的病理。令人兴奋的是，初步研究揭示了从系统性红斑狼疮（SLE）患者分离的免疫细胞中由几种SLAMF受体启动的信号通路的偏差。 项目#1的总体假设是小鼠受体Slamf 3、5和6及其同种型控制参与鼠狼疮发病机制的免疫应答。为检验这一假设而设计的实验分组如下： 具体目标#1：测试三种Slamf 6受体亚型启动狼疮不同的阳性和阴性调节途径的假设。 具体目标#2：测试Slamf 5受体在小鼠狼疮发病过程中控制T和B细胞以及DC中的信号传导的假设。 具体目标#3：检验Slamf 3受体启动信号传导控制自身抗体产生的假设。