Zawada Adam M, Zhang Lu, Emrich Insa E, Rogacev Kyrill S, Krezdorn Nicolas, Rotter Björn, Fliser Danilo, Devaux Yvan, Ziegler-Heitbrock Loems, Heine Gunnar H
Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.
Cardiovascular Research Unit, Luxembourg Institute of Health, Luxembourg.
Immunobiology. 2017 Jun;222(6):831-840. doi: 10.1016/j.imbio.2017.05.003. Epub 2017 May 31.
Among the three human monocyte subsets, intermediate CD14++CD16+ monocytes have been characterized as particularly proinflammatory cells in experimental studies and as potential biomarkers of cardiovascular risk in clinical cohorts. To further substantiate the distinct role of intermediate monocytes within human monocyte heterogeneity, we assessed subset-specific expression of miRNAs as central epigenetic regulators of gene expression. We hypothesized that intermediate monocytes have a distinct miRNA profile compared to classical and non-classical monocytes. By using small RNA-seq we analyzed 662 miRNAs in the three monocyte subsets. We identified 38 miRNAs that are differentially expressed in intermediate monocytes compared to both classical and non-classical monocytes with a p value of <10, of which two miRNAs - miR-6087 (upregulated) and miR-150-5p (downregulated) - differed in their expression more than ten-fold. Pathway analysis of the 38 differentially expressed miRNAs linked intermediate monocytes to distinct biological processes such as gene regulation, cell differentiation, toll-like receptor signaling as well as antigen processing and presentation. Moreover, differentially expressed miRNAs were connected to those genes that we previously identified as markers of intermediate monocytes. In aggregation, we provide first genome-wide miRNA data in the context of monocyte heterogeneity, which substantiate the concept of monocyte trichotomy in human immunity. The identification of miRNAs that are specific for intermediate monocytes may allow to develop strategies, which particularly target this cell population while sparing the other two subsets.
在三种人类单核细胞亚群中，中间型CD14++CD16+单核细胞在实验研究中被认为是特别具有促炎作用的细胞，并且在临床队列中是心血管风险的潜在生物标志物。为了进一步证实中间型单核细胞在人类单核细胞异质性中的独特作用，我们评估了作为基因表达核心表观遗传调节因子的miRNA的亚群特异性表达。我们假设中间型单核细胞与经典型和非经典型单核细胞相比具有独特的miRNA谱。通过使用小RNA测序，我们分析了三种单核细胞亚群中的662种miRNA。我们鉴定出38种在中间型单核细胞中与经典型和非经典型单核细胞相比差异表达的miRNA，其p值<10，其中两种miRNA——miR-6087（上调）和miR-150-5p（下调）——在表达上差异超过十倍。对这38种差异表达的miRNA进行通路分析，将中间型单核细胞与不同的生物学过程联系起来，如基因调控、细胞分化、Toll样受体信号传导以及抗原加工和呈递。此外，差异表达的miRNA与我们之前鉴定为中间型单核细胞标志物的那些基因相关。总的来说，我们在单核细胞异质性的背景下提供了首个全基因组miRNA数据，这证实了人类免疫中单核细胞三分法的概念。鉴定出对中间型单核细胞特异的miRNA可能有助于制定策略，特别针对这一细胞群体，同时 sparing 另外两个亚群。 （注：最后一个词“sparing”原文可能有误，推测为“sparing”，意为“使 spared 另外两个亚群”）
