Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Glia. 2013 Jan;61(1):91-103. doi: 10.1002/glia.22363. Epub 2012 May 31.
MicroRNAs (miRNAs) are a class of small (∼22 nucleotides) noncoding RNAs involved in the regulation of gene expression at the post-translational level. It is estimated that 30-90% of human genes are regulated by miRNAs, which makes these molecules of great importance for cell growth, activation, and differentiation. Microglia is CNS-resident cells of a myeloid lineage that play an important role in immune surveillance and are actively involved in many neurologic pathologies. Although the exact origin of microglia remains enigmatic, it is established that primitive macrophages from a yolk sac populate the brain and spinal cord in normal conditions throughout development. During various pathological events such as neuroinflammation, bone marrow derived myeloid cells also migrate into the CNS. Within the CNS, both primitive macrophages from the yolk sac and bone marrow derived myeloid cells acquire a specific phenotype upon interaction with other cell types within the CNS microenvironment. The factors that drive differentiation of progenitors into microglia and control the state of activation of microglia and bone marrow-derived myeloid cells within the CNS are not well understood. In this review we will summarize the role of miRNAs during activation and differentiation of myeloid cells. The role of miR-124 in the adaptation of microglia and macrophages to the CNS microenvironment will be further discussed. We will also summarize the role of miRNAs as modulators of activation of microglia and microphages. Finally, we will describe the role of miR-155 and miR-124 in the polarization of macrophages towards classically and alternatively activated phenotypes.
微小 RNA（miRNAs）是一类小的（约 22 个核苷酸）非编码 RNA，参与翻译后水平的基因表达调控。据估计，人类 30-90%的基因受到 miRNAs 的调控，这使得这些分子对细胞生长、激活和分化非常重要。小胶质细胞是中枢神经系统固有细胞，属于髓系，在免疫监视中发挥重要作用，并积极参与许多神经病理学。虽然小胶质细胞的确切起源仍然神秘，但已经确定，原始卵黄囊巨噬细胞在正常情况下会在发育过程中遍布大脑和脊髓。在神经炎症等各种病理事件中，骨髓来源的髓样细胞也会迁移到中枢神经系统。在中枢神经系统内，原始卵黄囊巨噬细胞和骨髓来源的髓样细胞在与中枢神经系统微环境中的其他细胞类型相互作用后获得特定表型。驱动祖细胞分化为小胶质细胞的因素以及控制小胶质细胞和骨髓来源的髓样细胞在中枢神经系统中的激活状态的因素尚未得到很好的理解。在这篇综述中，我们将总结 miRNAs 在髓样细胞激活和分化中的作用。将进一步讨论 miR-124 在小胶质细胞和巨噬细胞适应中枢神经系统微环境中的作用。我们还将总结 miRNAs 作为小胶质细胞和小吞噬细胞激活调节剂的作用。最后，我们将描述 miR-155 和 miR-124 在巨噬细胞向经典和交替激活表型极化中的作用。
