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Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells.
Immunity ( IF 25.5 ) Pub Date : 2019-08-29 , DOI: 10.1016/j.immuni.2019.08.008 Charles-Antoine Dutertre 1 , Etienne Becht 2 , Sergio Erdal Irac 1 , Ahad Khalilnezhad 3 , Vipin Narang 2 , Shabnam Khalilnezhad 2 , Pei Y Ng 2 , Lucas L van den Hoogen 4 , Jing Yao Leong 5 , Bernett Lee 2 , Marion Chevrier 2 , Xiao Meng Zhang 2 , Pearly Jean Ai Yong 6 , Geraldine Koh 2 , Josephine Lum 2 , Shanshan Wu Howland 2 , Esther Mok 2 , Jinmiao Chen 2 , Anis Larbi 2 , Henry Kun Kiaang Tan 7 , Tony Kiat Hon Lim 8 , Panagiota Karagianni 9 , Athanasios G Tzioufas 9 , Benoit Malleret 3 , Joshua Brody 10 , Salvatore Albani 5 , Joel van Roon 4 , Timothy Radstake 4 , Evan W Newell 2 , Florent Ginhoux 11
Immunity ( IF 25.5 ) Pub Date : 2019-08-29 , DOI: 10.1016/j.immuni.2019.08.008 Charles-Antoine Dutertre 1 , Etienne Becht 2 , Sergio Erdal Irac 1 , Ahad Khalilnezhad 3 , Vipin Narang 2 , Shabnam Khalilnezhad 2 , Pei Y Ng 2 , Lucas L van den Hoogen 4 , Jing Yao Leong 5 , Bernett Lee 2 , Marion Chevrier 2 , Xiao Meng Zhang 2 , Pearly Jean Ai Yong 6 , Geraldine Koh 2 , Josephine Lum 2 , Shanshan Wu Howland 2 , Esther Mok 2 , Jinmiao Chen 2 , Anis Larbi 2 , Henry Kun Kiaang Tan 7 , Tony Kiat Hon Lim 8 , Panagiota Karagianni 9 , Athanasios G Tzioufas 9 , Benoit Malleret 3 , Joshua Brody 10 , Salvatore Albani 5 , Joel van Roon 4 , Timothy Radstake 4 , Evan W Newell 2 , Florent Ginhoux 11
Affiliation
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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 FcεRIα 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.
中文翻译：
人单核吞噬细胞的单细胞分析揭示了亚组定义标志，并鉴定了循环性炎症树突状细胞。
人单核吞噬细胞包含表型和功能重叠的树突状细胞（DC）和单核细胞子集，但它们的异质性程度和用于子集识别的独特标记仍然难以捉摸。通过整合高维单细胞蛋白质和RNA表达数据，我们确定了不同的标志物来描绘常规DC2（cDC2s）中的单核细胞。对单核细胞使用CD88和CD89，对cDC2使用HLA-DQ和FcεRIα可以在血液和组织中进行特异性鉴定。我们还显示，基于CD5，CD163和CD14表达，cDC2可以细分为表型和功能上不同的子集，包括与先前定义的DC3相关的循环炎症CD5-CD163 + CD14 +细胞的不同子集。这些炎性DC3s在系统性红斑狼疮患者中扩增并与疾病活动相关。这些发现进一步揭示了健康和疾病中DC亚群的异质性，并可能为鉴定特定的DC亚群靶向疗法铺平道路。
更新日期：2019-08-29
中文翻译：
人单核吞噬细胞的单细胞分析揭示了亚组定义标志，并鉴定了循环性炎症树突状细胞。
人单核吞噬细胞包含表型和功能重叠的树突状细胞（DC）和单核细胞子集，但它们的异质性程度和用于子集识别的独特标记仍然难以捉摸。通过整合高维单细胞蛋白质和RNA表达数据，我们确定了不同的标志物来描绘常规DC2（cDC2s）中的单核细胞。对单核细胞使用CD88和CD89，对cDC2使用HLA-DQ和FcεRIα可以在血液和组织中进行特异性鉴定。我们还显示，基于CD5，CD163和CD14表达，cDC2可以细分为表型和功能上不同的子集，包括与先前定义的DC3相关的循环炎症CD5-CD163 + CD14 +细胞的不同子集。这些炎性DC3s在系统性红斑狼疮患者中扩增并与疾病活动相关。这些发现进一步揭示了健康和疾病中DC亚群的异质性，并可能为鉴定特定的DC亚群靶向疗法铺平道路。
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