T cell regulation by dendritic cells in EAE

描述(由申请人提供)：本建议书描述了一项为期5年的神经免疫学学术生涯发展培训计划。PI之前接受过神经科学培训，完成了神经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的科学技能。国际公认的免疫学权威Terri Laufer博士和Gary Koretzky博士将指导PI的科学发展。劳弗博士是一位风湿病临床科学家，因其在自身免疫方面的多项工作而备受推崇。科雷茨基博士是医学系研究副主席和病理学特聘教授，曾指导过许多学生、博士后研究员和初级教职员工。为了进一步促进研究人员的科学发展，一个由具有神经免疫学专业知识的知名医学科学家组成的咨询委员会，包括Francisco A. 冈萨雷斯-斯卡拉诺、史蒂文·雷纳、陈友海和迈克尔·K·拉克已经成立。这项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炎症性、脱髓鞘的中枢神经系统疾病。EAE所需的自身反应性CD4T细胞的产生过程尚不清楚。树突状细胞是一类特殊的抗原提呈细胞，能够激活CD4T细胞并启动广泛的效应功能。树突状细胞被认为在EAE的多个疾病阶段中起重要作用。因此，了解树突状细胞在EAE中的作用对于多发性硬化的发病机制具有特别重要的意义。鉴于这位导师在自身免疫中T细胞-树突状细胞相互作用方面的专业知识，劳弗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)明确EAE中树突状细胞依赖的CD4T细胞活化的机制；2)研究不同亚群的树突状细胞在EAE不同阶段的作用。研究设施的质量和赞助机构可用资源的多样性，再加上赞助商的智力和学术实力，为实施这一拟议的培训计划提供了理想的环境。

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.