Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
J Exp Med. 2011 Jun 6;208(6):1189-201. doi: 10.1084/jem.20101823. Epub 2011 May 9.
Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ∼22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation.
过度或不适当的免疫系统激活可能对机体有害,这需要多种分子机制来控制和适当终止免疫反应。微小 RNA(miRNA)是一种约 22 个核苷酸长的非编码 RNA,最近作为关键的转录后调控因子出现,调控多种生物学过程,包括对非自身的反应。在这项研究中,我们使用基因工程小鼠来研究 miR-146a 的生物学作用,并表明该基因的靶向缺失(其表达在免疫细胞成熟和/或激活后强烈上调)会导致多种免疫缺陷。总的来说,我们的研究结果表明,miR-146a 作为炎症、髓样细胞增殖和致癌转化的分子制动器发挥着关键作用。