title: SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset.
abstract: Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14(++)CD16(-), intermediate CD14(++)CD16(+), and nonclassical CD14(+)CD16(++) monocytes. Current knowledge on human monocyte heterogeneity is still incomplete: while it is increasingly acknowledged that CD14(++)CD16(+) monocytes are of outstanding significance in 2 global health issues, namely HIV-1 infection and atherosclerosis, CD14(++)CD16(+) monocytes remain the most poorly characterized subset so far. We therefore developed a method to purify the 3 monocyte subsets from human blood and analyzed their transcriptomes using SuperSAGE in combination with high-throughput sequencing. Analysis of 5 487 603 tags revealed unique identifiers of CD14(++)CD16(+) monocytes, delineating these cells from the 2 other monocyte subsets. Gene Ontology (GO) enrichment analysis suggests diverse immunologic functions, linking CD14(++)CD16(+) monocytes to Ag processing and presentation (eg, CD74, HLA-DR, IFI30, CTSB), to inflammation and monocyte activation (eg, TGFB1, AIF1, PTPN6), and to angiogenesis (eg, TIE2, CD105). In conclusion, we provide genetic evidence for a distinct role of CD14(++)CD16(+) monocytes in human immunity. After CD14(++)CD16(+) monocytes have earlier been discussed as a potential therapeutic target in inflammatory diseases, we are hopeful that our data will spur further research in the field of monocyte heterogeneity.
authors.affiliation: Department of Internal Medicine IV, Saarland University Hospital, Homburg/Saar, Germany.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
authors.forename: Kyrill S
authors.initials: KS
authors.lastname: Rogacev
authors.forename: Björn
authors.initials: B
authors.lastname: Rotter
authors.forename: Peter
authors.initials: P
authors.lastname: Winter
authors.forename: Rolf-R
authors.initials: RR
authors.lastname: Marell
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
mesh_terms: D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D020224:Expressed Sequence Tags; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000145:classification / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis
chemical_list: D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger