Mei Shiyue, Liu Yu, Wu Xue, He Qingsheng, Min Siping, Li Ling, Zhang Yuan, Yang Rongcun
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China.
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China
J Leukoc Biol. 2016 Feb;99(2):301-10. doi: 10.1189/jlb.1A0115-032RR. Epub 2015 Sep 1.
Immune cell-lineage specification and function are influenced by progenitor origin and environmental factors. The mechanism of differentiation of immune cells, such as neutrophils, monocytes, and myeloid-derived suppressor cells, in inflammatory environments has not been elucidated completely. In this study, we have identified human microRNA-136 as a positive regulator of the differentiation of granulocytes and monocytes. Ectopic microRNA-136 induced cells to express higher levels of CD11b, CD14, and C/EBPε, secrete more cytokines, and synthesize higher levels of reactive oxygen species and H(2)O(2). microRNA-136 was shown to target and degrade multiple differentiation-associated molecules, such as the transcription factor NFIA, which induced the release of another microRNA, microRNA-223, with the ability to promote CD11b expression. Furthermore, microRNA-136 expression was remarkably increased by TNF-α, which activated NF-κB to bind to the DNA-promoter region controlling microRNA-136 expression. Additionally, TNF-α may alter NFIA expression through its modulation of microRNA-136 expression. Thus, TNF-α-mediated microRNA-136 may play a critical role in the generation and differentiation of inflammatory immune cells.
免疫细胞谱系的确定和功能受祖细胞来源和环境因素的影响。中性粒细胞、单核细胞和髓源性抑制细胞等免疫细胞在炎症环境中的分化机制尚未完全阐明。在本研究中，我们确定了人类微小RNA-136是粒细胞和单核细胞分化的正向调节因子。异位表达微小RNA-136可诱导细胞表达更高水平的CD11b、CD14和C/EBPε，分泌更多细胞因子，并合成更高水平的活性氧和H2O2。微小RNA-136可靶向并降解多种与分化相关的分子，如转录因子NFIA，后者可诱导另一种具有促进CD11b表达能力的微小RNA——微小RNA-223的释放。此外，TNF-α可显著增加微小RNA-136的表达，TNF-α激活NF-κB使其结合到控制微小RNA-136表达的DNA启动子区域。另外，TNF-α可能通过调节微小RNA-136的表达来改变NFIA的表达。因此，TNF-α介导的微小RNA-136可能在炎症免疫细胞的产生和分化中起关键作用。
