immunopathogenesis of NMO-IgG and AQP4-specific T cells in neuromyelitis optica

描述（由申请人提供）：这是一份由美国国家神经疾病和中风研究所（NINDS）颁发的为期5年的K08指导临床科学家研究职业发展奖的提案，旨在研究NMO-IgG和水通道蛋白-4特异性T细胞在光学神经脊髓炎免疫发病机制中的作用。视神经脊髓炎（NMO）是一种针对视神经和脊髓的破坏性神经炎症性疾病，可导致失明和瘫痪。NMO与一种血清学生物标志物NMO- igg相关，其靶向中枢神经系统星形胶质细胞端足的水通道蛋白-4 （AQP4）水通道。本基金旨在从三个方面阐明神经脊髓炎的免疫发病机制：1。表征NMO- igg通过募集粒细胞诱导或加重NMO疾病表型的作用，2。2 .利用特异性抗AQP4抗体鉴定脊髓和视神经中AQP4的NMO-IgG靶点；评估AQP4特异性Th17细胞在引发和促进炎症中的作用

DESCRIPTION (provided by applicant): This is a proposal for a 5-year K08 Mentored Clinical Scientist Research Career Development Award from the National Institutes of Neurological Disease and Stroke (NINDS) to investigate the role of NMO-IgG and Aquaporin-4 specific T cells in the immunopathogenesis of neuromyelitis optical. Neuromyelitis optical (NMO) is a devastating neuroinflammatory disorder targeting the optic nerves and spinal cord leading to blindness and paralysis. NMO is associated with a serologic biomarker, the NMO-IgG, which targets the aquaporin-4 (AQP4) water channel on the end feet of astrocytes in the central nervous system. This grant is designed to elucidate the immunopathogenesis of neuromyelitis optical focusing on three aspects: 1. Characterizing the role of the NMO-IgG in inducing or exacerbating the NMO disease phenotype by recruiting granulocytes, 2. Identifying the target of the NMO-IgG on AQP4 in the spinal cord and optic nerves using specific anti-AQP4 antibodies, 3. Evaluating the role of Th17 cells specific for AQP4 in instigating and facilitating inflammation in the central nervous system. Each aim is complimentary to the whole project and will provide unique insights into the pathogenesis of NMO. The principle investigator for this project is Michael Levy, MD, PhD, and an Assistant Professor in the Department of Neurology at the Johns Hopkins University who is working under the mentorship of Peter Calabresi, MD, Professor and Director of the Division of Neuroimmunology at Johns Hopkins University. Dr. Calabresi is a leader in the clinical and research fields of multiple sclerosis and neuroimmunologic diseases. Together in one of the nation's most productive research environments, Dr. Levy will have 75% protected time to spend in the lab and use the rest of the time to translate his basic science work to the bedside in the NMO clinic and on the inpatient neurology service at Johns Hopkins Hospital.