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

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. Overall design: Mouse Lung Interstitial Macrophages single cell mRNA profiles

巨噬细胞（Macrophages）是一类异质性细胞群体，参与组织稳态维持、炎症反应及多种病理进程。尽管主要的组织驻留巨噬细胞群已被广泛研究，但定位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开展了系统研究。我们鉴定出两类跨组织保守存在的独立间质巨噬细胞亚群：Lyve1loMHCIIhiCX3CR1hi（简称为Lyve1loMHCIIhi）与Lyve1hiMHCIIloCX3CR1lo（简称为Lyve1hiMHCIIlo）单核细胞来源型间质巨噬细胞，二者具有截然不同的基因表达谱、表型特征、功能特性及定位模式。通过采用可诱导性巨噬细胞耗竭小鼠模型（SLCO2B1-DTR），我们发现Lyve1hiMHCIIlo间质巨噬细胞的缺失会加剧实验性肺纤维化。综上，本研究证实跨组织中存在两类独立的间质巨噬细胞群体，且其功能编程呈现保守的微环境依赖性。整体实验设计：小鼠肺间质巨噬细胞单细胞mRNA表达谱。