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-猫眼课题宝

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：

8845267

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

项目类别：

财政年份：

2013

资助国家：

美国

项目状态：

已结题

起止时间：

2013-05-01 至 2016-04-30

来源：

https://reporter.nih.gov/project-details/8845267

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 Health 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 research study targeted treatment water channel young woman

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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.

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