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. Mouse Lung Interstitial Macrophages single cell mRNA profiles