SLAM Gene Family Controlled Pathways to SLE

SLAM 基因家族控制 SLE 通路

• 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
• 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

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在鼠和人SLE中人和小鼠SLAMF 4-SLAMF 2受体/配体相互作用的功能分析。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。