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

描述(由申请人提供)：这是一项为期5年的K08临床科学家导师研究职业发展奖的提案，该奖项由美国国立神经疾病和中风研究所(NINDS)颁发，旨在调查NMO-IgG和Aquaporin-4特异性T细胞在视神经脊髓炎免疫发病机制中的作用。视神经脊髓炎(NMO)是一种以视神经和脊髓为靶点的破坏性神经炎性疾病，可导致失明和瘫痪。NMO与一种血清学生物标志物NMO-Ig G有关，NMO-Ig G靶向中枢神经系统星形胶质细胞末端足部的水通道AQP4。本研究旨在从三个方面阐明神经脊髓炎的免疫发病机制：1.研究NMO-Ig G通过募集粒细胞诱导或加重NMO病表型的作用；2.用特异性抗AQP4抗体确定脊髓和视神经AQP4上NMO-Ig G的靶点；3.评价AQP4特异性Th17细胞在炎症中的作用 在中枢神经系统中。每个目标都是对整个项目的补充，并将为NMO的发病机制提供独特的见解。该项目的首席研究员是Michael Levy，医学博士，约翰霍普金斯大学神经学系助理教授，在约翰霍普金斯大学神经免疫学系主任、教授兼医学博士Peter Calabresi的指导下工作。卡拉布雷西博士是多发性硬化症和神经免疫学疾病临床和研究领域的领导者。在美国生产率最高的研究环境之一中，利维博士将有75%的受保护时间花在实验室里，剩下的时间用来将他的基础科学工作转移到NMO诊所的床边和约翰·霍普金斯医院的住院神经科服务上。

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.