Two distinct interstitial macrophage populations coexist across tissues in unique subtissular niches [FACs sorted]

Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation and in multiple pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within 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: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localisation. Using a mouse model of inducible macrophage depletion (SLCO2B1-DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs exist across tissues and exhibit conserved niche-dependent functional programming. FACS sorted cells from several animals

巨噬细胞（Macrophages）是一类异质性细胞群，参与组织稳态维持、炎症反应及多种病理进程。尽管目前已对主要的组织驻留巨噬细胞群开展了广泛研究，但定居于组织实质内的间质巨噬细胞（interstitial macrophages，IMs）的相关认知仍较为匮乏。本研究针对小鼠肺、脂肪、心脏及真皮组织中的间质巨噬细胞展开了探究，鉴定出两类在不同组织中保守存在的独立间质巨噬细胞亚群：Lyve1loMHCIIhiCX3CR1hi（简称Lyve1loMHCIIhi）与Lyve1hiMHCIIloCX3CR1lo（简称Lyve1hiMHCIIlo）单核细胞来源间质巨噬细胞，二者具有截然不同的基因表达谱、表型、功能及组织定位。本研究借助可诱导性巨噬细胞耗竭小鼠模型（SLCO2B1-DTR）发现，Lyve1hiMHCIIlo亚群的缺失会加重实验性肺纤维化。综上，本研究证实不同组织中均存在两类独立的间质巨噬细胞亚群，且它们呈现出保守的微环境依赖性功能编程特征。来自多只动物的荧光激活细胞分选（Fluorescence-Activated Cell Sorting，FACS）分选细胞。