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

• 批准号: 10196298
• 负责人: Brian Todd Edelson
• 金额: $ 23.63万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10196298
• 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

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.

摘要 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 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， 我们意外地发现了MS患者脑脊液（CSF）中循环的小胶质细胞。 假设CSF小胶质细胞是表现出神经系统疾病特有特征内源性CNS细胞 states.我们的目的是确定任何疾病相关的特征的CSF小胶质细胞。我们将探索 流式细胞术检测MS患者脑脊液小胶质细胞的免疫学特征。为了探索分子 在各种疾病状态下的CSF小胶质细胞的特征，我们将对分选的 CSF小胶质细胞。将比较不同年龄组CSF小胶质细胞的基因表达模式， MS与健康对照受试者的比较，以确定这些细胞的健康和疾病特异性特征。 最后，我们将在MS中通过流式细胞术和转录组学分析进行免疫表型分析。 患者治疗前后这一提议将为一部小说的人物塑造奠定基础 能够调节CNS免疫的细胞群。