SLAM Gene Family Controlled Pathways to SLE

SLAM 基因家族控制 SLE 通路

基本信息

批准号：
8513250
负责人：
CORNELIS P TERHORST
金额：
$ 151.41万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
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/8513250
关键词：
Address Adhesions Advisory Committees Affect Alleles Alternative Splicing Amino Acid Sequence Amino Acids Antibody Avidity Antigen Presentation Apoptosis Arthralgia Autoantibodies Autoimmune Diseases Autoimmune Process Autoimmunity B-Lymphocytes Basic Science Binding Binding Sites Biological Markers CD28 gene CD3 Antigens CD4 Positive T Lymphocytes CD44 gene Cell Communication Cell physiology Cell surface Cells Chromosomes, Human, Pair 1 Chronic Clinical Code Complement Complementary DNA Complex Congenic Mice Cytoplasmic Tail Data Dendritic Cells Diagnostic Disease Disease susceptibility Event Exanthema Fatigue Female of child bearing age Funding Gene Family Gene Transfer Techniques Genes Genetic Genetic Engineering Genetic Polymorphism Goals Haplotypes Hereditary Disease Human Immune Immune response Immunity Immunobiology Immunoglobulin G Immunologic Receptors Immunosuppressive Agents Inbred BALB C Mice Individual Infection Institution Interleukin-17 Interleukin-2 Investigation Israel Kidney Knockout Mice Lead Leadership Ligands Lupus Medical Medical center Membrane Microbiology Molecular Monitor Monoclonal Antibodies Mononuclear Mouse Strains Mus Nephritis Nuclear Outcome Outcome Study Pathogenesis Pathology Pathway interactions Patients Phagocytes Pharmaceutical Preparations Phenotype Phosphorylation Play Production Productivity Progress Reports Property Protein Isoforms Reaction Receptor Gene Refuse Disposal Reporting Research Research Personnel Role SLAM family receptor Signal Transduction Spliced Genes Strategic Planning Surface Surface Antigens Synapses System Systemic Lupus Erythematosus T-Lymphocyte T-Lymphocyte Subsets Testing Therapeutic To autoantigen Transgenes Transgenic Organisms Translational Research Treatment Protocols Tyrosine Variant Work X Chromosome base cytokine disorder risk human disease indexing innovation insight medical schools member memory CD4 T lymphocyte microbial mouse model novel programs promoter receptor research study sensor src Homology Region 2 Domain tool

项目摘要

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）：该应用程序寻求支持阐明SLAMF受体在系统性红斑狼疮（SLE）发病机理中的作用，其最终目标是开发基于SLAMF的治疗策略，可以应用于SLE患者。由于我们对来自SLE患者的细胞的研究结果以及我们对遗传改变的小鼠的令人兴奋的发现，这些细胞会发展出与狼疮相关的自身免疫性，我们现在已经建立了剖析SLAMF受体如何启动的细胞相互作用机制和信号传导的系统，从而有助于对自动抗原和人类病原体的耐受性控制。这些见解和工具是计划项目申请的基础，标题为：三个相互联系的项目和两个辅助核心的“ SLAM家庭受体控制的途径”。项目＃1 SLAMF，SLAMF5和SLAMF6受体诱导的鼠狼疮途径。 PL：Cox Terhorst，贝丝以色列执事医疗中心。项目＃2对鼠和人SLE中的人和小鼠SLAMF4“ SLAMF2受体 /配体相互作用的功能分析。PL：哈佛医学院微生物学和免疫生物学系Arlene Sharpe。 PL：乔治·托索科斯（George Tsokos），贝丝（Beth）以色列女执事医疗中心。核心遗传小鼠核心。中心核心B行政核心。