Single-cell immune landscape of human atherosclerotic plaques
Single-cell immune landscape of human atherosclerotic plaques
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DOI：
10.1038/s41591-019-0590-4
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发表时间：
2019-10-01
期刊：
影响因子：
82.9
通讯作者：
Giannarelli, Chiara
中科院分区：
文献类型：
--
作者：
Fernandez, Dawn M.;Rahman, Adeeb H.;Giannarelli, Chiara
动脉粥样硬化是由免疫系统在循环和血管病灶部位的多方面贡献驱动的。然而，动脉粥样硬化病变内免疫细胞失调导致缺血性中风或心肌梗死等临床事件的具体特征知之甚少。在这里，使用单细胞蛋白质组学和转录组学分析，我们发现了具有临床症状性疾病（近期卒中或短暂性脑缺血发作）的患者与无症状性疾病（近期无卒中）患者颈动脉斑块中T细胞和巨噬细胞的不同特征。来自有症状患者的斑块的特征在于CD 4（+）T细胞的不同亚群和活化和分化的T细胞。此外，这些斑块中的一些T细胞亚群呈现T细胞耗竭的标志物。此外，来自这些斑块的巨噬细胞含有交替活化的表型，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，并显示出白细胞介素-1 β信号传导的证据。识别与脑血管事件相关的斑块中先天性和适应性免疫细胞的特定特征，可以设计更精确的心血管免疫疗法。
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 beta 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.