Single-cell omics reveal human mononuclear phagocyte heterogeneity and inflammatory DC in health and disease. Single-cell omics reveal human mononuclear phagocyte heterogeneity and inflammatory DC in health and disease

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DC) and monocytes, but their identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we clearly delineated monocytes from conventional DC2 (cDC2), identifying new markers including CD88/CD89 for monocytes and HLA-DQ/FcRI for cDC2, allowing their unambiguous characterization in blood and tissues. We also show that cDC2 can be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163 and CD14 expression, including a unique subset of circulating inflammatory CD5-CD163+CD14+ cells related to previously defined DC3. These inflammatory DC3 were expanded in systemic lupus erythematosus patients, correlating with disease activity. Unravelling the heterogeneity of DC sub-populations in health and disease paves the way for specific DC subset-targeting therapies. Overall design: Indexed single cell RNAseq (scRNAseq) of human peripheral blood dendritic cells and monocytes

人类单核吞噬细胞（mononuclear phagocytes）由表型与功能存在重叠的树突状细胞（dendritic cells, DC）和单核细胞亚群组成，但其精准鉴定仍颇具难度。
本研究通过整合高维单细胞蛋白与RNA表达谱数据，成功将单核细胞与经典DC2（conventional DC2, cDC2）明确区分开来，鉴定出单核细胞的新型标志物CD88/CD89以及cDC2的新型标志物HLA-DQ/FcεRIα，从而实现二者在血液与组织中的精准鉴定。
研究还发现，基于CD5、CD163与CD14的表达模式，cDC2可进一步划分为表型与功能各异的亚群，其中包括一类独特的循环炎性CD5⁻CD163⁺CD14⁺细胞亚群，该亚群与此前定义的DC3密切相关。
这类炎性DC3亚群在系统性红斑狼疮（systemic lupus erythematosus）患者体内发生扩增，且与疾病活动度呈显著正相关。
阐明健康与疾病状态下DC亚群的异质性，可为靶向特定DC亚群的治疗策略奠定重要基础。
实验整体设计：针对人类外周血树突状细胞与单核细胞开展索引单细胞RNA测序（single cell RNAseq, scRNAseq）。