SLAM Gene Family Controlled Pathways to SLE

描述（由申请人提供）： 本申请寻求对阐明SLAMF受体在系统性红斑狼疮（SLE）发病机制中的作用的支持，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我们对发生狼疮相关自身免疫的转基因小鼠的令人兴奋的发现，我们现在有系统来剖析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。这些见解和工具是一个名为“SLAM家庭接收者控制的SLE路径”的计划项目应用程序的基础，用于三个相互关联的项目和两个支持核心。项目#1 SlamfS，Slamf 5和Slamf 6受体诱导的小鼠狼疮途径。PL：考克斯特霍斯特，贝斯以色列女执事医疗中心。项目#2人类和小鼠SLAMF 4的功能分析小鼠和人类SLE中SLAMF 2受体/配体相互作用。PL：阿琳·夏普，微生物学和免疫生物学系，哈佛医学院。项目#3 SLE免疫细胞中人SLAMF受体的功能。 PL：乔治·索科斯，贝斯以色列女执事医疗中心。核心A基因小鼠核心。PL：王宁海，贝斯以色列女执事医疗。中心核心B行政核心。PL考克斯特霍斯特，贝丝以色列女执事医疗中心。

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.