Innate immune regulation of neuroinflammation

神经炎症的先天免疫调节

基本信息

批准号：
10410555
负责人：
Gregory F Sonnenberg
金额：
$ 61.05万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10410555
关键词：
Address Affect Age Age-associated memory impairment Alzheimer&apos s Disease American Amyotrophic Lateral Sclerosis Antigen Presentation Antigen Targeting Antigens Autoimmune B-Lymphocytes Blood Circulation CD4 Positive T Lymphocytes Cell Maturation Cells Clinical Clinical Research Coculture Techniques Cognitive Critical Pathways Cytokine Receptors Data Demyelinating Diseases Dendritic Cells Disease Exhibits Experimental Models Family Gene Expression Profile Health Care Costs Histocompatibility Antigens Class II Homing Immunity In Vitro Infiltration Inflammation Inflammatory Innate Immune System Interleukin-17 Intestines Knowledge Lymphocyte Lymphoid Cell Mediating Multiple Sclerosis Mus Myelin Neuraxis Neurodegenerative Disorders Parkinson Disease Pathogenesis Pathway interactions Patients Peripheral Population Production Regulation Research Proposals Role Sampling Specific qualifier value T cell response T-Lymphocyte Testing Therapeutic Tissues Translating Translations adaptive immunity cell growth regulation cell type curative treatments cytokine immunoregulation in vivo innovation mouse model mucosal site multiple sclerosis patient neuroinflammation next generation novel novel strategies prevent progenitor receptor response tool transcription factor treatment strategy

项目摘要

PROJECT ABSTRACT Inflammation in the central nervous system (CNS) is causally associated with the pathogenesis and progression of multiple demyelinating and neurodegenerative diseases, including Multiple Sclerosis (MS), Parkinson's Disease, Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and general age-associated cognitive decline Therefore, there is an urgent need to develop novel approaches to prevent, limit or reverse neuroinflammation. Basic, translation and clinical studies indicate that T cells can be major drivers of inflammation in the CNS, but the mechanisms promoting or inhibiting these responses remain poorly defined. The fundamental focus of this research proposal is to: (i) interrogate a novel pathway by which the innate immune system controls T cell responses in the CNS, (ii) understand the regulation of these cellular interactions, and (iii) define whether it is possible to harness this or related pathways for therapeutic benefit in neuroinflammation. We will employ innovative approaches and develop new tools to address these fundamental gaps in knowledge, and where possible, translate our findings from mice into clinically defined patient samples. Results from these studies will advance our understanding of the pathways that promote or inhibit pro-inflammatory T cell responses in the CNS, and could provoke the next generation of novel preventative, therapeutic or curative treatment strategies for demyelinating and neurodegenerative diseases.

项目摘要中枢神经系统（CNS）的炎症与发病机理和多种脱髓鞘和神经退行性疾病的进展，包括多发性硬化症（MS），帕金森氏病，阿尔茨海默氏病，肌萎缩性侧索硬化症以及一般年龄相关的因此，认知能力下降，迫切需要开发新颖的方法来预防，限制或逆转神经炎症。基本，翻译和临床研究表明，T细胞可以是中枢神经系统的炎症，但是促进或抑制这些反应的机制仍然很差。该研究建议的基本重点是：（i）询问一种新颖的途径先天免疫系统控制中枢神经系统中的T细胞反应，（ii）了解这些调节细胞相互作用，（iii）定义是否可以利用此途径或相关的途径神经炎症的治疗益处。我们将采用创新方法，并开发新工具解决这些知识中的这些基本差距，并在可能的情况下将我们的发现从老鼠转化为临床定义的患者样品。这些研究的结果将提高我们对促进或抑制中枢神经系统中促炎的T细胞反应的途径，可能会引起下一代新型预防，治疗或治疗治疗策略和神经退行性疾病。