title: Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets.
abstract: New official nomenclature subdivides human monocytes into 3 subsets: the classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), and nonclassical (CD14(+)CD16(++)) monocytes. This introduces new challenges, as monocyte heterogeneity is mostly understood based on 2 subsets, the CD16(-) and CD16(+) monocytes. Here, we comprehensively defined the 3 circulating human monocyte subsets using microarray, flow cytometry, and cytokine production analysis. We find that intermediate monocytes expressed a large majority (87%) of genes and surface proteins at levels between classical and nonclassical monocytes. This establishes their intermediary nature at the molecular level. We unveil the close relationship between the intermediate and nonclassic monocytes, along with features that separate them. Intermediate monocytes expressed highest levels of major histocompatibility complex class II, GFRα2 and CLEC10A, whereas nonclassic monocytes were distinguished by cytoskeleton rearrangement genes, inflammatory cytokine production, and CD294 and Siglec10 surface expression. In addition, we identify new features for classic monocytes, including AP-1 transcription factor genes, CLEC4D and IL-13Rα1 surface expression. We also find circumstantial evidence supporting the developmental relationship between the 3 subsets, including gradual changes in maturation genes and surface markers. By comprehensively defining the 3 monocyte subsets during healthy conditions, we facilitate target identification and detailed analyses of aberrations that may occur to monocyte subsets during diseases.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore. wong_kok_loon@immunol.a-star.edu.sg
authors.forename: Kok Loon
authors.initials: KL
authors.lastname: Wong
authors.forename: June Jing-Yi
authors.initials: JJ
authors.lastname: Tai
authors.forename: Wing-Cheong
authors.initials: WC
authors.lastname: Wong
authors.forename: Hao
authors.initials: H
authors.lastname: Han
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Sem
authors.forename: Wei-Hseun
authors.initials: WH
authors.lastname: Yeap
authors.forename: Philippe
authors.initials: P
authors.lastname: Kourilsky
authors.forename: Siew-Cheng
authors.initials: SC
authors.lastname: Wong
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D016000:Cluster Analysis; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D046228:Microarray Analysis; D008954:Models, Biological; D009000:Monocytes / Q000145:classification* / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D054928:Validation Studies as Topic