Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Cell. 2019 Sep 5;178(6):1509-1525.e19. doi: 10.1016/j.cell.2019.08.009.
Most tissue-resident macrophage (RTM) populations are seeded by waves of embryonic hematopoiesis and are self-maintained independently of a bone marrow contribution during adulthood. A proportion of RTMs, however, is constantly replaced by blood monocytes, and their functions compared to embryonic RTMs remain unclear. The kinetics and extent of the contribution of circulating monocytes to RTM replacement during homeostasis, inflammation, and disease are highly debated. Here, we identified Ms4a3 as a specific gene expressed by granulocyte-monocyte progenitors (GMPs) and subsequently generated Ms4a3 reporter, Ms4a3, and Ms4a3 fate-mapping models. These models traced efficiently monocytes and granulocytes, but no lymphocytes or tissue dendritic cells. Using these models, we precisely quantified the contribution of monocytes to the RTM pool during homeostasis and inflammation. The unambiguous identification of monocyte-derived cells will permit future studies of their function under any condition.
大多数组织驻留巨噬细胞（RTM）群体是由胚胎造血的波播种的，并在成年期独立于骨髓贡献自我维持。然而，一部分 RTM 不断被循环单核细胞取代，其功能与胚胎 RTM 仍不清楚。在稳态、炎症和疾病期间，循环单核细胞对 RTM 替代的贡献的动力学和程度存在很大争议。在这里，我们确定 Ms4a3 是粒细胞-单核细胞祖细胞（GMP）表达的特定基因，随后生成了 Ms4a3 报告基因、Ms4a3 和 Ms4a3 命运映射模型。这些模型有效地追踪了单核细胞和粒细胞，但没有追踪淋巴细胞或组织树突状细胞。使用这些模型，我们精确地量化了单核细胞在稳态和炎症期间对 RTM 池的贡献。单核细胞衍生细胞的明确鉴定将允许在任何条件下对其功能进行未来研究。
