Immunologic Characterization of CSF microglia in multiple sclerosis

多发性硬化症脑脊液小胶质细胞的免疫学特征

基本信息

批准号：
10374170
负责人：
Brian Todd Edelson
金额：
$ 19.69万
依托单位：
WASHINGTON UNIVERSITY
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：
2021-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10374170
关键词：
Address Aftercare American Automobile Driving Axon Biopsy Blood Circulation Cell Count Cell Separation Cells Central Nervous System Diseases Cerebrospinal Fluid Characteristics Chronic Complex Dendritic Cells Diagnosis Disease Disease Progression Elements Exhibits Flow Cytometry Functional disorder Gene Expression Gene Expression Profile Gene Expression Profiling Health Human Immune Immune system Immunity Immunologic Markers Immunologics Individual Inflammation Inflammatory Informatics Injury Investigation Knowledge Mediating Membrane Proteins Methods Microglia Molecular Profiling Monitor Multiple Sclerosis Myelin Myeloid Cells Nature Nerve Nerve Degeneration Neuraxis Neurologic Newly Diagnosed Patients Peripheral Phagocytosis Phenotype Population Process Recurrent disease Relapse Relapsing-Remitting Multiple Sclerosis Resolution Secondary Progressive Multiple Sclerosis Sum T cell regulation T cell response Techniques Therapeutic Time Tissue-Specific Gene Expression Tissues Yolk Sac axon injury base central nervous system demyelinating disorder cerebrospinal fluid flow disability injury and repair monocyte multiple sclerosis patient nervous system disorder neuroinflammation neuropathology next generation novel protein expression repaired response to injury single-cell RNA sequencing trait transcriptome transcriptome sequencing transcriptomics

项目摘要

ABSTRACT Microglia are long-lived, self-replicating, yolk sac-derived immune cells of the central nervous system (CNS) parenchyma that are critical modulators of immunity and neuropathology. Microglia dysfunction contributes to several neurologic diseases, including multiple sclerosis (MS). In our preliminary studies, we have unexpectedly identified microglia circulating with the cerebrospinal fluid (CSF) of patients with MS. We hypothesize that CSF microglia are endogenous CNS cells that exhibit signatures unique to neurologic disease states. We aim to identify any disease-associated characteristics of CSF microglia. We will explore the number and immunologic features of CSF microglia in MS by flow cytometric analysis. To explore the molecular signature of CSF microglia in various disease states, we will perform single cell RNA sequencing on sorted CSF microglial cells. Comparisons will be made between gene expression patterns in CSF microglia between MS in relation to healthy control subjects to determine the health- and disease-specific profile of these cells. Finally, we will pursue immunologic phenotyping both by flow cytometry and transcriptomic analysis in MS patients before and after treatment. This proposal will lay the groundwork for the characterization of a novel cellular population capable of regulating CNS immunity.

抽象的小胶质细胞是中枢神经系统 (CNS) 的长寿、自我复制、卵黄囊衍生的免疫细胞实质是免疫和神经病理学的关键调节剂。小胶质细胞功能障碍有助于多种神经系统疾病，包括多发性硬化症 (MS)。在我们的初步研究中，我们有出乎意料地发现了多发性硬化症患者脑脊液（CSF）中循环的小胶质细胞。我们假设脑脊液小胶质细胞是内源性中枢神经系统细胞，表现出神经系统疾病特有的特征州。我们的目标是确定脑脊液小胶质细胞的任何与疾病相关的特征。我们将探索这个数字通过流式细胞术分析 MS 中脑脊液小胶质细胞的免疫学特征。探索分子脑脊液小胶质细胞在各种疾病状态下的特征，我们将对分选的单细胞 RNA 进行测序脑脊液小胶质细胞。将比较脑脊液小胶质细胞中的基因表达模式 MS 与健康对照受试者相关，以确定这些细胞的健康和疾病特异性概况。最后，我们将通过流式细胞术和 MS 转录组分析进行免疫表型分析患者在治疗前和治疗后。该提案将为小说的人物塑造奠定基础能够调节中枢神经系统免疫的细胞群。