title: MicroRNA profiling of human intermediate monocytes.
abstract: 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 <10-10, 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.
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
authors.affiliation: Cardiovascular Research Unit, Luxembourg Institute of Health, Luxembourg.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.
authors.forename: Insa E
authors.initials: IE
authors.lastname: Emrich
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany; University Heart Center Luebeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine), University Hospital Schleswig-Holstein, Luebeck, Germany.
authors.forename: Kyrill S
authors.initials: KS
authors.lastname: Rogacev
authors.affiliation: GenXPro GmbH, Frankfurt/Main, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Krezdorn
authors.affiliation: GenXPro GmbH, Frankfurt/Main, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Rotter
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Cardiovascular Research Unit, Luxembourg Institute of Health, Luxembourg.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Devaux
authors.affiliation: EvA Study Center, Comprehensive Pneumology Center Helmholtz Zentrum Muenchen - German Research Center for Environmental Health, Gauting, Germany.
authors.forename: Loems
authors.initials: L
authors.lastname: Ziegler-Heitbrock
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: Gunnar.Heine@uks.eu.
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
mesh_terms: D015415:Biomarkers; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015723:Gene Library; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016130:Immunophenotyping; D035683:MicroRNAs / Q000235:genetics*; D058977:Molecular Sequence Annotation; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: CD14; CD16; Monocyte subsets; miRNAs