Immunologic Characterization of CSF microglia in multiple sclerosis

摘要 小胶质细胞是中枢神经系统(CNS)卵黄囊来源的长寿、自我复制的免疫细胞。 实质是免疫和神经病理的关键调节器。小胶质细胞功能障碍导致 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 WE患者脑脊液中意外发现循环中的小胶质细胞 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 各州。我们的目标是确定任何与脑脊液小胶质细胞相关的疾病特征。我们将探索这个数字 流式细胞仪分析MS患者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不同疾病状态下的特征，我们将对分选的 脑脊液小胶质细胞。将比较脑脊液小胶质细胞的基因表达模式 以确定这些细胞在健康和疾病方面的特征。 最后，我们将通过流式细胞术和转录分析对多发性硬化症进行免疫学表型鉴定。 治疗前和治疗后的患者。这一提议将为小说的人物塑造奠定基础。 具有调节中枢神经系统免疫功能的细胞群。

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.