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长寿的，自我复制的，蛋黄囊的免疫细胞（CNS）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几种神经系统疾病，包括多发性硬化症（MS）。在我们的初步研究中，我们有出乎意料地鉴定出MS患者的脑脊液（CSF）循环的小胶质细胞。我们假设CSF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独有的特征国家。我们旨在确定CSF小胶质细胞的任何相关特征。我们将探索数字通过流式细胞仪分析，CSF小胶质细胞的免疫学特征。探索分子 CSF小胶质细胞在各种疾病状态下的签名，我们将对排序进行单细胞RNA测序 CSF小胶质细胞。将在CSF小胶质细胞中的基因表达模式之间进行比较 MS与健康对照受试者有关，以确定这些细胞的健康和疾病特异性特征。最后，我们将通过MS中的流式细胞术和转录组分析来追求免疫表型治疗前后的患者。该提议将为小说的特征奠定基础能够调节中枢神经系统免疫力的细胞种群。