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首页> 外文期刊>Journal of neuroinflammation >Innate Immunity in multiple sclerosis white matter lesions: expression of natural cytotoxicity triggering receptor 1 (NCR1)
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Innate Immunity in multiple sclerosis white matter lesions: expression of natural cytotoxicity triggering receptor 1 (NCR1)

机译：多发性硬化症白质病变的先天免疫：天然细胞毒性触发受体1（NCR1）的表达

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Background Pathogenic or regulatory effects of natural killer (NK) cells are implicated in many autoimmune diseases, but evidence in multiple sclerosis (MS) and its murine models remains equivocal. In an effort to illuminate this, we have here analysed expression of the prototypic NK cell marker, NCR1 (natural cytotoxicity triggering receptor; NKp46; CD335), an activating receptor expressed by virtually all NK cells and therefore considered a pan-marker for NK cells. The only definitive ligand of NCR1 is influenza haemagglutinin, though there are believed to be others. In this study, we investigated whether there were differences in NCR1+ cells in the peripheral blood of MS patients and whether NCR1+ cells are present in white matter lesions. Results We first investigated the expression of NCR1 on peripheral blood mononuclear cells and found no significant difference between healthy controls and MS patients. We then investigated mRNA levels in central nervous system (CNS) tissue from MS patients: NCR1 transcripts were increased more than 5 times in active disease lesions. However when we performed immunohistochemical staining of this tissue, few NCR1+ NK cells were identified. Rather, the major part of NCR1 expression was localised to astrocytes, and was considerably more pronounced in MS patients than controls. In order to further validate de novo expression of NCR1 in astrocytes, we used an in vitro staining of the human astrocytoma U251 cell line grown to model whether cell stress could be associated with expression of NCR1. We found up-regulation of NCR1 expression in U251 cells at both the mRNA and protein levels. Conclusions The data presented here show very limited expression of NCR1+ NK cells in MS lesions, the majority of NCR1 expression being accounted for by expression on astrocytes. This is compatible with a role of this cell-type and NCR1 ligand/receptor interactions in the innate immune response in the CNS in MS patients. This is the first report of NCR1 expression on astrocytes in MS tissue: it will now be important to unravel the nature of cellular interactions and signalling mediated through innate receptor expression on astrocytes.
机译：背景技术自然杀伤（NK）细胞的致病性或调节作用与许多自身免疫性疾病有关，但多发性硬化症（MS）及其鼠模型的证据仍然不明确。为了阐明这一点，我们在这里分析了原型NK细胞标记物NCR1（天然细胞毒性触发受体; NKp46; CD335）的表达，该受体实际上是所有NK细胞表达的激活受体，因此被认为是NK细胞的泛标记。 。 NCR1的唯一确定性配体是流感血凝素，尽管据信还有其他配体。在这项研究中，我们调查了MS患者外周血中NCR1 +细胞是否存在差异，以及白质病灶中是否存在NCR1 +细胞。结果我们首先研究了NCR1在外周血单个核细胞上的表达，发现健康对照组和MS患者之间无显着差异。然后，我们调查了MS患者中枢神经系统（CNS）组织中的mRNA水平：在活动性疾病病变中，NCR1转录本增加了5倍以上。但是，当我们对该组织进行免疫组织化学染色时，几乎没有NCR1 + NK细胞被鉴定出来。而是，NCR1表达的主要部分定位于星形胶质细胞，在MS患者中比在对照组中更为明显。为了进一步验证NCR1在星形胶质细胞中的从头表达，我们使用了人星形细胞瘤U251细胞系的体外染色来模拟细胞应激是否与NCR1的表达有关。我们发现U251细胞中mRNA和蛋白质水平的NCR1表达上调。结论此处提供的数据显示NCR1 + NK细胞在MS病变中的表达非常有限，其中大部分NCR1表达是由星形胶质细胞上的表达引起的。这与MS患者中枢神经系统先天免疫反应中这种细胞类型和NCR1配体/受体相互作用的作用是相容的。这是NCR1在MS组织中星形胶质细胞上表达的第一个报道：现在，阐明星形胶质细胞上先天受体表达介导的细胞相互作用和信号传导的性质将很重要。

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