T cell regulation by dendritic cells in EAE

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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.