Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets
Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets
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DOI：
10.1182/blood-2010-12-326355
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发表时间：
2011-08-04
期刊：
影响因子：
20.3
通讯作者：
Wong, Siew-Cheng
中科院分区：
文献类型：
--
作者：
Wong, Kok Loon;Tai, June Jing-Yi;Wong, Siew-Cheng
新的官方命名法将人单核细胞细分为3个亚群：经典(CD14(++)CD16(-))，中间(CD14（++)CD16(+)）和非经典(CD14（+)CD16(++)）单核细胞。这带来了新的挑战，因为单核细胞异质性主要基于两个亚群，CD16（-）和CD16（+）单核细胞来理解。在这里，我们使用微阵列、流式细胞术和细胞因子产生分析全面定义了3个循环的人类单核细胞亚群。我们发现中间单核细胞在经典和非经典单核细胞之间表达了绝大多数（87%）的基因和表面蛋白。这就确定了它们在分子水平上的中介性质。我们揭示了中间和非经典单核细胞之间的密切关系，以及区分它们的特征。中间型单核细胞表达最高水平的主要组织相容性复合体II类、GFR α 2和CLEC10A，而非经典型单核细胞通过细胞骨架重排基因、炎症细胞因子产生、CD294和Siglec10表面表达来区分。此外，我们还发现了经典单核细胞的新特征，包括AP-1转录因子基因、cle4d和IL-13R α 1表面表达。我们还发现了支持这三个亚群之间发育关系的间接证据，包括成熟基因和表面标记的逐渐变化。通过全面定义健康状态下的3个单核细胞亚群，我们促进了目标识别和详细分析单核细胞亚群在疾病期间可能发生的畸变。(血。2011;118 (5):e16-e31)
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, GFR alpha 2 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-13R alpha 1 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)