Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore; Program in Emerging Infectious Disease, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore.
Immunity. 2019 Sep 17;51(3):573-589.e8. doi: 10.1016/j.immuni.2019.08.008. Epub 2019 Aug 29.
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 CD5CD163CD14 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.
人类单核吞噬细胞包括表型和功能上重叠的树突状细胞 (DC) 和单核细胞亚群，但它们的异质性程度和亚群鉴定的独特标志物仍不清楚。通过整合高维单细胞蛋白和 RNA 表达数据，我们确定了独特的标志物来区分单核细胞和传统 DC2 (cDC2)。使用 CD88 和 CD89 来区分单核细胞，使用 HLA-DQ 和 FcεRIα 来区分 cDC2，可在血液和组织中对其进行特异性识别。我们还表明，cDC2 可以根据 CD5、CD163 和 CD14 的表达进一步细分为表型和功能不同的亚群，包括与之前定义的 DC3 相关的循环炎症性 CD5CD163CD14 细胞的独特亚群。这些炎症性 DC3 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，并可能为特定的 DC 亚群靶向治疗的鉴定铺平道路。
