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动脉粥样硬化斑块单细胞免疫图谱问世
2019-10-09 10:59

人类动脉粥样硬化斑块的单细胞免疫图谱,近期由美国西奈山伊坎医学院Chiara Giannarelli课题组绘制。该研究2019年10月7日在线发表于国际一流学术期刊《自然—医学》。

使用单细胞蛋白质组学和转录组学分析,研究人员发现与无症状疾病(近期无卒中)相比,临床症状疾病(近期卒中或短暂性脑缺血发作)患者颈动脉斑块中T细胞和巨噬细胞均具有明显特征。来自有症状患者的斑块的特征在于CD4阳性T细胞的独特亚群以及被激活和分化的T细胞。而且,这些斑块中的一些T细胞亚群表现出T细胞衰竭的标志物。另外,来自这些斑块的巨噬细胞包含交替激活的表型,包括与斑块易损性相关的亚群。在无症状患者的斑块中,T细胞和巨噬细胞被激活并显示出白介素-1β信号的证据。在与脑血管事件有关的斑块中先天性和适应性免疫细胞特定特征的鉴定让设计更精确的心血管免疫疗法成为可能。

据悉,动脉粥样硬化是由循环系统内和血管局灶性部位的免疫系统多方面影响导致的。然而,人们对动脉粥样硬化病变内导致临床事件,如缺血性中风或心肌梗塞的免疫细胞失调的具体特征了解甚少。

附:英文原文

Title: Single-cell immune landscape of human atherosclerotic plaques

Author: Dawn M. Fernandez, Adeeb H. Rahman, Nicolas F. Fernandez, Aleksey Chudnovskiy, El-ad David Amir, Letizia Amadori, Nayaab S. Khan, Christine K. Wong, Roza Shamailova, Christopher A. Hill, Zichen Wang, Romain Remark, Jennifer R. Li, Christian Pina, Christopher Faries, Ahmed J. Awad, Noah Moss, Johan L. M. Bjorkegren, Seunghee Kim-Schulze, Sacha Gnjatic, Avi Maayan, J Mocco, Peter Faries, Miriam Merad, Chiara Giannarelli

Issue&Volume: 2019-10-07

Abstract: Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. However, specific characteristics of dysregulated immune cells within atherosclerotic lesions that lead to clinical events such as ischemic stroke or myocardial infarction are poorly understood. Here, using single-cell proteomic and transcriptomic analyses, we uncovered distinct features of both T cells and macrophages in carotid artery plaques of patients with clinically symptomatic disease (recent stroke or transient ischemic attack) compared to asymptomatic disease (no recent stroke). Plaques from symptomatic patients were characterized by a distinct subset of CD4+ T cells and by T cells that were activated and differentiated. Moreover, some T cell subsets in these plaques presented markers of T cell exhaustion. Additionally, macrophages from these plaques contained alternatively activated phenotypes, including subsets associated with plaque vulnerability. In plaques from asymptomatic patients, T cells and macrophages were activated and displayed evidence of interleukin-1 signaling. The identification of specific features of innate and adaptive immune cells in plaques that are associated with cerebrovascular events may enable the design of more precisely tailored cardiovascular immunotherapies. Single-cell proteomic and transcriptional profiling of atherosclerotic lesions from human carotid arteries reveals specific features of lesional T cells and macrophages associated with symptomatic disease.

DOI: 10.1038/s41591-019-0590-4

Source:https://www.nature.com/articles/s41591-019-0590-4

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:87.241
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章:《自然—医学》:Online/在线发表

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