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

NMO-IgG 和 AQP4 特异性 T 细胞在视神经脊髓炎中的免疫发病机制

• 批准号: 8509867
• 负责人: Michael Levy
• 金额: $ 19.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509867
• 关键词: African American; Animal Model; Antibodies; Applications Grants; Astrocytes; Basic Science; Binding; Binding Sites; Biological Markers; Blindness; Blocking Antibodies; Blood - brain barrier anatomy; Brain; Cell Communication; Cells; Chronic; Clinic; Clinical; Clinical Research; Complement-Dependent Cytotoxicity; Disease; Doctor of Philosophy; Environment; Epitopes; Ethnic Origin; Experimental Autoimmune Encephalomyelitis; Genetic Engineering; Grant; Helper-Inducer T-Lymphocyte; Hospitals; IgG1; Immune; Immune Targeting; Immunoglobulin Class Switching; Immunoglobulin G; Incidence; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Inpatients; Institutes; K-Series Research Career Programs; Knockout Mice; Mediating; Mentors; Mentorship; Mission; Multiple Sclerosis; Mus; National Institute of Neurological Disorders and Stroke; Nervous system structure; Neuraxis; Neurologic; Neurology; Neuromyelitis Optica; Optic Nerve; Optics; Paralysed; Pathogenesis; Pathogenicity; Pathologic; Pathology; Patients; Peptides; Phenotype; Population; Prevalence; Reaction; Recruitment Activity; Relapse; Research; Research Activity; Research Personnel; Rest; Risk; Rodent Model; Role; Scientist; Series; Serological; Services; Societies; Spinal; Spinal Cord; Staging; Stroke; T-Cell Immunologic Specificity; T-Lymphocyte; Testing; Therapeutic Intervention; Time; Tissues; Translating; Transverse Myelitis; United States; Universities; Wild Type Mouse; Work; age group; aquaporin 4; body system; design; disease phenotype; extracellular; foot; granulocyte; insight; nervous system disorder; neuroimmunologic disease; neuroimmunology; prevent; professor; public health relevance; research study; water channel; young woman

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.

描述（由申请人提供）：这是美国国立神经疾病和中风研究所（NINDS）颁发的为期5年的K 08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细胞在视神经肌萎缩症免疫发病机制中的作用。视神经肌萎缩症（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与血清学生物标志物NMO-IgG相关，NMO-IgG靶向中枢神经系统星形胶质细胞末端足上的水通道蛋白-4（AQP 4）水通道。本基金旨在阐明光学神经肌病的免疫发病机制，主要集中在三个方面：1。表征NMO-IgG在通过募集粒细胞诱导或加重NMO疾病表型中的作用，2.使用特异性抗AQP 4抗体鉴定脊髓和视神经中AQP 4上的NMO-IgG的靶点，3.评估AQP 4特异性Th 17细胞在激发和促进炎症中的作用 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。该项目的主要研究者是约翰霍普金斯大学神经病学系的Michael Levy医学博士和助理教授，他在约翰霍普金斯大学神经免疫学系主任Peter Calabresi医学博士的指导下工作。Calabresi博士是多发性硬化症和神经免疫疾病临床和研究领域的领导者。在全国最富有成效的研究环境之一，Levy博士将有75%的保护时间花在实验室，并利用剩余的时间将他的基础科学工作转化为NMO诊所的床边和约翰霍普金斯医院的住院神经病学服务。