Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Brain and Systems Immunology Laboratory, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Immunity. 2024 Jun 11;57(6):1225-1242.e6. doi: 10.1016/j.immuni.2024.04.019. Epub 2024 May 14.
Classical monocytes (CMs) are ephemeral myeloid immune cells that circulate in the blood. Emerging evidence suggests that CMs can have distinct ontogeny and originate from either granulocyte-monocyte- or monocyte-dendritic-cell progenitors (GMPs or MDPs). Here, we report surface markers that allowed segregation of murine GMP- and MDP-derived CMs, i.e., GMP-Mo and MDP-Mo, as well as their functional characterization, including fate definition following adoptive cell transfer. GMP-Mo and MDP-Mo yielded an equal increase in homeostatic CM progeny, such as blood-resident non-classical monocytes and gut macrophages; however, these cells differentially seeded various other selected tissues, including the dura mater and lung. Specifically, GMP-Mo and MDP-Mo differentiated into distinct interstitial lung macrophages, linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide evidence for the existence of two functionally distinct CM subsets in the mouse that differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge.
经典单核细胞（Classical monocytes，CMs）是短暂存在的髓系免疫细胞，在血液中循环。新出现的证据表明，CMs 可能具有不同的发生和起源，可以来自粒细胞-单核细胞或单核细胞-树突状细胞前体（granulocyte-monocyte- or monocyte-dendritic-cell progenitors，GMPs 或 MDPs）。在这里，我们报告了表面标志物，这些标志物允许分离鼠 GMP 和 MDP 来源的 CMs，即 GMP-Mo 和 MDP-Mo，以及它们的功能特征，包括通过过继细胞转移后的命运定义。GMP-Mo 和 MDP-Mo 产生了等量的稳态 CM 祖细胞增加，如血液驻留的非经典单核细胞和肠道巨噬细胞；然而，这些细胞在不同的其他选定组织中定植，包括硬脑膜和肺。具体而言，GMP-Mo 和 MDP-Mo 分化为不同的间质性肺巨噬细胞，将 CM 二分法与先前报道的肺巨噬细胞异质性联系起来。总的来说，我们提供了证据证明在小鼠中存在两种功能不同的 CM 亚群，它们在稳态和挑战后对周围组织巨噬细胞群体的贡献不同。
