T cell regulation by dendritic cells in EAE

EAE 中树突状细胞对 T 细胞的调节

• 批准号: 7588318
• 负责人: Gregory Wu
• 金额: $ 17.26万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588318
• 关键词: Address; Advisory Committees; Anatomy; Animal Model; Antigen Presentation; Antigen-Presenting Cells; Antigens; Autoimmune Process; Autoimmune Responses; Autoimmunity; CD4 Positive T Lymphocytes; Cell Communication; Chronic; Class; Clinical Skills; Complex; Demyelinations; Dendritic Cells; Development; Disease; Encephalomyelitis; Environment; Experimental Autoimmune Encephalomyelitis; Faculty; Goals; Histocompatibility; Immune; Immune Targeting; Immunization; Immunology; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Institution; Kinetics; Laboratories; Mediating; Medical; Medicine; Mentors; Methods; Modeling; Multiple Sclerosis; Mus; Myelin; Neuraxis; Neurology; Neurosciences; Pathogenesis; Pathology; Pattern; Peptides; Phase; Phenotype; Population; Postdoctoral Fellow; Predisposition; Process; Program Development; Property; Proteins; Research; Research Personnel; Residencies; Resources; Rest; Rheumatology; Role; Role playing therapy; Scientist; Staging; Students; Surface Antigens; T cell regulation; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Testing; Thinking; Time; Tissues; Training; Training Programs; Work; authority; base; career; cell motility; central nervous system demyelinating disorder; cytokine; irradiation; macrophage; member; monocyte; neuroimmunology; professor; research facility; research study; response; skills; trafficking

DESCRIPTION (provided by applicant): This proposal describes a 5-year training program for the development of an academic career in neuroimmunology. The PI has previous training in neuroscience, completed formal residency training in neurology, and is currently expanding his clinical skills in multiple sclerosis and scientific skills in neuroimmunology research. Drs. Terri Laufer and Gary Koretzky, internationally recognized authorities in immunology, will mentor the Pi's scientific development. Dr. Laufer is a rheumatology clinician-scientist well regarded for her diverse work in autoimmunity. Dr. Koretzky, the Vice Chair for Research in the Department of Medicine and endowed Professor in Pathology, has mentored numerous students, post-doctoral fellows and junior faculty members. To further promote the investigator's scientific development, an Advisory Committee comprising highly regarded medical scientists with expertise in neuroimmunology, including Drs. Francisco A. Gonzalez-Scarano, Steven Reiner, Youhai Chen and Michael K. Racke, has been established. The proposed research focuses on the role of dendritic cells in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system. The process involved in generating the auto-reactive CD4 T cells required for EAE is unclear. Dendritic cells are a special class of antigen presenting cell capable of activating CD4 T cells and initiating a wide array of effector functions. Dendritic cells are thought to be important during multiple phases of disease in EAE. Therefore, understanding the contributions of dendritic cells to EAE is of particular relevance to the pathogenesis of multiple sclerosis. Given the mentor's expertise in T cell-dendritic cell interactions in autoimmunity, Dr. Laufer's laboratory is the ideal setting to study the precise roles played dendritic cells during inflammatory responses targeting the central nervous system. Specific aims include: 1) defining the mechanisms for dendritic cell-dependent CD4 T cell activation in EAE, and 2) studying the contributions of different subsets of dendritic cells during various phases of EAE. The quality of the research facilities and the diversity of the resources available at the sponsoring institution, in combination with the intellectual and academic strength of the sponsors, provide an ideal environment in which to conduct this proposed training program.

描述（由申请人提供）：本提案描述了一个为期5年的培训计划，用于发展神经免疫学的学术生涯。PI之前接受过神经科学培训，完成了神经病学的正式住院医师培训，目前正在扩展他在多发性硬化症方面的临床技能和神经免疫学研究方面的科学技能。Terri Laufer博士和加里Koretzky博士是国际公认的免疫学权威，他们将指导Pi的科学发展。Laufer博士是一位风湿病学临床科学家，因其在自身免疫方面的各种工作而备受赞誉。Koretzky博士是医学系研究副主任和病理学教授，指导了许多学生，博士后研究员和初级教师。为了进一步促进研究者的科学发展，一个咨询委员会由在神经免疫学方面具有专长的高度知名的医学科学家组成，包括弗朗西斯科博士。 Gonzalez-Scarano，Steven Reiner，Youhai Chen和Michael K. Racke，已经成立。拟议的研究重点是树突状细胞在实验性自身免疫性脑脊髓炎（EAE）中的作用，EAE是多发性硬化症的模型。多发性硬化症是一种中枢神经系统的炎性脱髓鞘疾病。EAE所需的自身反应性CD 4 T细胞的产生过程尚不清楚。树突状细胞是一类特殊的抗原呈递细胞，能够激活CD 4 T细胞并启动广泛的效应子功能。树突状细胞被认为在EAE疾病的多个阶段中是重要的。因此，了解树突状细胞对EAE的贡献与多发性硬化的发病机制特别相关。鉴于导师在自身免疫中T细胞-树突状细胞相互作用方面的专业知识，Laufer博士的实验室是研究树突状细胞在针对中枢神经系统的炎症反应中所扮演的确切角色的理想环境。具体目标包括：1）确定EAE中树突状细胞依赖性CD 4 T细胞活化的机制，以及2）研究树突状细胞的不同亚群在EAE的各个阶段中的贡献。研究设施的质量和赞助机构可用资源的多样性，以及赞助商的智力和学术实力，为开展这项拟议的培训计划提供了理想的环境。