Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells
Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells
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DOI：
10.1016/j.immuni.2019.08.008
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发表时间：
2019-09-17
期刊：
影响因子：
32.4
通讯作者：
Ginhoux, Florent
中科院分区：
文献类型：
--
作者：
Dutertre, Charles-Antoine;Becht, Etienne;Ginhoux, Florent
人类单核吞噬细胞包括树突状细胞（dc）和单核细胞的表型和功能重叠的亚群，但它们的异质性程度和亚群识别的独特标记仍然难以捉摸。通过整合高维单细胞蛋白和RNA表达数据，我们确定了不同的标记来区分单核细胞和常规DC2 （cDC2s）。单核细胞使用CD88和CD89， cDC2s使用HLA-DQ和Fc epsilon RI α，可以在血液和组织中进行特异性鉴定。我们还发现，cDC2s可以根据CD5、CD163和CD14的表达细分为表型和功能上不同的亚群，包括与先前定义的DC3s相关的循环炎性CD5(-)CD163(+)CD14（+）细胞的不同亚群。这些炎性dc3在系统性红斑狼疮患者中扩大，并与疾病活动性相关。这些发现进一步揭示了DC亚群在健康和疾病中的异质性，并可能为确定特定的DC亚群靶向治疗铺平道路。
Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and Fc epsilon RI alpha for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5(-)CD163(+)CD14(+) cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies.