Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches
Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches
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DOI：
10.1126/science.aau0964
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发表时间：
2019-03-15
期刊：
影响因子：
56.9
通讯作者：
Ginhoux, Florent
中科院分区：
文献类型：
--
作者：
Chakarov, Svetoslav;Lim, Hwee Ying;Ginhoux, Florent
巨噬细胞是参与组织稳态、炎症和各种病理的异质细胞群。虽然主要的组织驻留巨噬细胞群体已被广泛研究，间质巨噬细胞（IM）驻留在组织实质内仍然定义不清。在这里，我们研究了来自小鼠肺、脂肪、心脏和真皮的IM。我们确定了两个独立的IM亚群，它们在组织中是保守的：Lyve 1（lo）MHCII（hi）CX 3CR 1（hi）（Lyve 1（lo）MHCII（hi））和Lyve 1（hi）MHCII（lo）CX 3CR 1（lo）（Lyve 1（hi）MHCII（lo））单核细胞衍生的IM，具有不同的基因表达谱、表型、功能和定位。使用一种新的小鼠诱导型巨噬细胞耗竭模型（Slco 2b 1（flox/DTR）），我们发现Lyve 1（hi）MHCII（lo）IM的缺失加剧了实验性肺纤维化。因此，我们证明了两个独立的群体的IM跨组织共存，并表现出保守的小生境依赖的功能编程。
Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation, and various pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within the tissue parenchyma remain poorly defined. Here we studied IMs from murine lung, fat, heart, and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1(lo)MHCII(hi)CX3CR1(hi) (Lyve1(lo)MHCII(hi)) and Lyve1(hi)MHCII(lo)CX3CR1(lo) (Lyve1(hi)MHCII(lo)) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion (Slco2b1(flox/DTR)), we found that the absence of Lyve1(hi)MHCII(lo) IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming.