Phenotype, function, and differentiation potential of human monocyte subsets.
Phenotype, function, and differentiation potential of human monocyte subsets.
复制标题
DOI：
10.1371/journal.pone.0176460
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Metes DM
中科院分区：
文献类型：
--
作者：
Boyette LB;Macedo C;Hadi K;Elinoff BD;Walters JT;Ramaswami B;Chalasani G;Taboas JM;Lakkis FG;Metes DM
人类单核细胞分为经典（CD14++CD16−）、非经典（CD14dimCD16++）和中间（CD14++CD16+）亚群。关于这些亚型补体的正常功能和变异，特别是它们向树突状细胞（DC）或巨噬细胞分化的潜力的记载仍然不完整。因此，我们对健康受试者外周血中的单核细胞进行了表型分析，并对高速分类亚群进行了功能研究。研究发现，随着时间的推移和个体的不同，子集频率受到严格控制。在TLR激动剂的作用下，不同亚群的TNFα、IL-6和IL-1β的分泌不同，经典单核细胞分泌最多，非经典单核细胞分泌最少。单核细胞，特别是非经典亚型的单核细胞，在细胞内TLR3刺激下分泌干扰素-α (IFN-α)。经IL-4和GM-CSF孵育后，经典单核细胞获得了单核细胞来源的DC （mo-DC）标记物和形态，并刺激了MLR中异体T细胞的增殖；中间和非经典单核细胞则没有。与IL-3和Flt3配体孵育后，没有亚群分化为浆细胞样DC。经GM-CSF （M1诱导）或巨噬细胞集落刺激因子（M-CSF） （M2诱导）孵育后，所有亚群均获得巨噬细胞形态，分泌巨噬细胞相关细胞因子，并表现出增强的吞噬能力。从这些研究中我们得出结论，经典单核细胞是mo- dc的主要来源，但所有亚群都可以分化为巨噬细胞。我们还发现，单核细胞，特别是非经典亚群，是响应病毒相关TLR激动剂分泌I型IFN的另一种来源。
Human monocytes have been grouped into classical (CD14++CD16−), non-classical (CD14dimCD16++), and intermediate (CD14++CD16+) subsets. Documentation of normal function and variation in this complement of subtypes, particularly their differentiation potential to dendritic cells (DC) or macrophages, remains incomplete. We therefore phenotyped monocytes from peripheral blood of healthy subjects and performed functional studies on high-speed sorted subsets. Subset frequencies were found to be tightly controlled over time and across individuals. Subsets were distinct in their secretion of TNFα, IL-6, and IL-1β in response to TLR agonists, with classical monocytes being the most producers and non-classical monocytes the least. Monocytes, particularly those of the non-classical subtype, secreted interferon-α (IFN-α) in response to intracellular TLR3 stimulation. After incubation with IL-4 and GM-CSF, classical monocytes acquired monocyte-derived DC (mo-DC) markers and morphology and stimulated allogeneic T cell proliferation in MLR; intermediate and non-classical monocytes did not. After incubation with IL-3 and Flt3 ligand, no subset differentiated to plasmacytoid DC. After incubation with GM-CSF (M1 induction) or macrophage colony-stimulating factor (M-CSF) (M2 induction), all subsets acquired macrophage morphology, secreted macrophage-associated cytokines, and displayed enhanced phagocytosis. From these studies we conclude that classical monocytes are the principal source of mo-DCs, but all subsets can differentiate to macrophages. We also found that monocytes, in particular the non-classical subset, represent an alternate source of type I IFN secretion in response to virus-associated TLR agonists.