Brain Ischemia Significantly Alters microRNA Expression in Human Peripheral Blood Natural Killer Cells
Brain Ischemia Significantly Alters microRNA Expression in Human Peripheral Blood Natural Killer Cells
复制标题
脑缺血显着改变人外周血自然杀伤细胞中的 microRNA 表达
DOI：
10.3389/fimmu.2020.00759
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发表时间：
2020-05-14
影响因子：
7.3
通讯作者：
Zhang, Xiao-An
中科院分区：
文献类型：
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作者：
Kong, Ying;Li, Shiyao;Zhang, Xiao-An
脑缺血诱导全身免疫抑制并增加宿主对感染的易感性。microRNAs（miRNAs）是免疫细胞中的分子开关，但miRNAs在人类免疫细胞中对脑缺血反应的改变及其对免疫防御的影响仍然难以捉摸。自然杀伤（NK）细胞对于宿主对病原体的早期防御至关重要。在这项研究中，我们确定了减少计数，细胞因子的产生，并在人外周血NK细胞从急性缺血性中风患者获得的细胞毒性。NK细胞数量和活性的丧失程度与梗死体积相关。microRNA测序分析显示，脑缺血显著改变了循环NK细胞中的miRNA表达谱，其中miRNA-451 a和miRNA-122- 5 p显著上调。重要的是，miR-451 a或miR-122- 5 p的抑制增强了NK细胞中活化相关受体的表达。这些结果提供了脑缺血改变人类NK细胞中miRNA特征的第一个证据。
Brain ischemia induces systemic immunosuppression and increases a host's susceptibility to infection. MicroRNAs (miRNAs) are molecular switches in immune cells, but the alterations of miRNAs in human immune cells in response to brain ischemia and their impact on immune defense remain elusive. Natural killer (NK) cells are critical for early host defenses against pathogens. In this study, we identified reduced counts, cytokine production, and cytotoxicity in human peripheral blood NK cells obtained from patients with acute ischemic stroke. The extent of NK cell loss of number and activity was associated with infarct volume. MicroRNA sequencing analysis revealed that brain ischemia significantly altered miRNA expression profiles in circulating NK cells, in which miRNA-451a and miRNA-122-5p were dramatically upregulated. Importantly, inhibition of miR-451a or miR-122-5p augmented the expression of activation-associated receptors in NK cells. These results provide the first evidence that brain ischemia alters miRNA signatures in human NK cells.