Lab of Tumor Suppressor Genes and MiRNAs, Institute of Medical Science, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
Immunol Lett. 2012 Apr 30;143(2):208-17. doi: 10.1016/j.imlet.2012.02.014.
Natural killer (NK) cells are an important component of the innate immune system that recognizes and kills virally infected and malignant cells. MicroRNAs (miRNAs) are short non-coding RNAs that have emerged as critical regulators of gene expression in immune cells. However, very little is known about miRNAs involved in human NK cell activation. In this study, we sequenced 4 small RNA libraries from one inactivated and three activated human NK cells treated with cytokines interleukin-2 (IL-2), IL-15 and IL-21, respectively, by using the Illumina high-throughput sequencing technology. We identified a total of 440, 458, 475 and 452 known mature miRNAs in resting and IL-2, IL-15 and IL-21 activated human NK cells, respectively. Among these, we found a few miRNAs including miR-155, miR-15a, miR-1246 and miR-331-3p with consistent differential expression in all three activated human NK cells by IL-2, IL15 or IL-21, which was confirmed by quantitative real-time PCR. Furthermore, our results revealed that them iRNA-155 over-expression enhanced while the miRNA-155 antagonist impaired the NK cell-mediated killing activity, indicating that miRNA-155 plays an important role in the control of NK cell cytotoxicity.This is the first time we showed the microRNA transcriptomes and differentially expressed miRNAs involved in human NK cell activation by IL-2, IL-15 and IL-21 stimulation, which provides valuable clues for the further elucidation of microRNA regulation in human NK cell activation and may have a great potential in NK cell immunotherapy.
自然杀伤 (NK) 细胞是先天免疫系统的重要组成部分，可识别并杀死病毒感染和恶性细胞。微小 RNA (miRNA) 是短的非编码 RNA，已成为免疫细胞中基因表达的关键调节因子。然而，人们对参与人类 NK 细胞激活的 miRNA 知之甚少。在这项研究中，我们使用 Illumina 高通量测序技术，分别对 1 个失活和 3 个经细胞因子白细胞介素-2 (IL-2)、IL-15 和 IL-21 处理激活的人 NK 细胞的 4 个小 RNA 文库进行了测序。我们总共在静息和经 IL-2、IL-15 和 IL-21 激活的人 NK 细胞中分别鉴定出 440、458、475 和 452 个已知成熟 miRNA。其中，我们发现了一些 miRNA，包括 miR-155、miR-15a、miR-1246 和 miR-331-3p，它们在所有三种经 IL-2、IL15 或 IL-21 激活的人 NK 细胞中表达一致，这通过定量实时 PCR 得到了验证。此外，我们的结果表明，miRNA-155 的过表达增强了 NK 细胞介导的杀伤活性，而 miRNA-155 拮抗剂则削弱了 NK 细胞介导的杀伤活性，表明 miRNA-155 在控制 NK 细胞细胞毒性中发挥重要作用。这是我们首次展示了涉及 IL-2、IL-15 和 IL-21 刺激的人 NK 细胞激活的 miRNA 转录组和差异表达 miRNA，为进一步阐明 miRNA 在人 NK 细胞激活中的调节作用提供了有价值的线索，并可能在 NK 细胞免疫治疗中有很大的潜力。
