SLAM Gene Family Controlled Pathways to SLE

SLAM 基因家族控制 SLE 通路

• 批准号: 8890069
• 负责人: CORNELIS P TERHORST
• 金额: $ 161.08万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8890069
• 关键词: Autoimmunity; Biological Markers; Cell Communication; Cells; Complement; Diagnostic; Disease; Gene Family; Genetic; Goals; Human; Immune; Immunobiology; Immunosuppressive Agents; Israel; Lead; Ligands; Lupus; Medical; Medical center; Microbiology; Monitor; Mus; Outcome; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Role; SLAM family receptor; Signal Transduction; System; Systemic Lupus Erythematosus; Therapeutic; To autoantigen; Treatment Protocols; base; indexing; insight; medical schools; novel; programs; receptor; research study; tool

DESCRIPTION (provided by applicant): This application seeks support for elucidating the role of the SLAMF receptors in the pathogenesis of Systemic Lupus Erythematosus (SLE) with the ultimate goal to develop SLAMF-based therapeutic strategies that can be applied to SLE patients. Because of the outcomes of our studies with cells derived from SLE patients and our exciting findings with genetically altered mice, which develop lupus-related autoimmunity, we now have the systems in place to dissect how cell interaction mechanisms and signaling initiated by the SLAMF receptors contribute to the control of tolerance to autoantigens and to the pathogenesis of human SLE. These insights and tools are the basis for a Program Project application entitled: "SLAM FAMILY RECEPTOR CONTROLLED PATHWAYS TO SLE" for three interlinked projects and two supporting Cores. Project #1 The SlamfS, Slamf5 and Slamf6 receptor-induced pathways to murine lupus. PL: Cox Terhorst, Beth Israel Deaconess Medical Center. Project #2 Functional analyses of human and mouse SLAMF4"SLAMF2 receptor / ligand interactions in murine and human SLE. PL: Arlene Sharpe, Department of Microbiology and Immunobiology, Harvard Medical School. Project #3 Function of human SLAMF receptors in SLE immune cells. PL: George Tsokos, Beth Israel Deaconess Medical Center. Core A Genetic Mouse Core.PL: Ninghai Wang, Beth Israel Deaconess Medical. Center Core B Administrative Core.PL Cox Terhorst, Beth Israel Deaconess Medical Center.

描述（由申请人提供）： 本申请寻求支持阐明 SLAMF 受体在系统性红斑狼疮 (SLE) 发病机制中的作用，最终目标是开发可应用于 SLE 患者的基于 SLAMF 的治疗策略。由于我们对 SLE 患者细胞的研究结果以及对产生狼疮相关自身免疫的基因改造小鼠的令人兴奋的发现，我们现在拥有适当的系统来剖析 SLAMF 受体启动的细胞相互作用机制和信号传导如何有助于控制对自身抗原的耐受性和人类 SLE 的发病机制。这些见解和工具是题为“SLAM 家族受体控制的 SLE 途径”的项目应用程序的基础，该项目应用程序涉及三个相互关联的项目和两个支持核心。项目#1 SlamfS、Slamf5 和 Slamf6 受体诱导的小鼠狼疮途径。 PL：Cox Terhorst，贝斯以色列女执事医疗中心。项目 #2 小鼠和人类 SLE 中人类和小鼠 SLAMF4"SLAMF2 受体/配体相互作用的功能分析。PL：Arlene Sharpe，哈佛医学院微生物学和免疫生物学系。项目 #3 人类 SLAMF 受体在 SLE 免疫细胞中的功能。 PL：George Tsokos，贝斯以色列女执事医疗中心。 Core A 基因小鼠 Core.PL：Ninghai Wang，Beth Israel Deaconess Medical。中心核心 B 行政核心。PL Cox Terhorst，贝斯以色列女执事医疗中心。