Identification of microRNA transcriptome involved in human natural killer cell activation

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 940, 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 the miRNA-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. (c) 2012 Elsevier B.V. All rights reserved.