Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets New official nomenclature subdivides human monocytes into 3 subsets: the classical (CD14 CD16 ), intermediate (CD14 CD16 ), and nonclassical (CD14 CD16 ) monocytes

Abstract

This introduces new challenges, as monocyte het-erogeneity is mostly understood based on 2 subsets, the CD16 and CD16 mono-cytes. 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 histocom-patibility complex class II, GFR2 and CLEC10A, whereas nonclassic mono-cytes were distinguished by cytoskeleton rearrangement genes, inflammatory cyto-kine 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-13R1 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. (Blood. 2011; 118(5):e16-e31)