Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches

Abstract

2017 © The Authors. 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.