Understanding the Heterogeneity of Resident Liver Macrophages

Abstract

Resident tissue macrophages (RTMs) are cells with a high functional plasticity assuming pleiotropic roles in their tissue of residence, from clearance of dead cells and metabolic sensing in steady state to cytokine production and tissue repair during inflammation. The liver has long been considered as only populated by Kupffer cells (KCs), a macrophage population assumed to be in charge of all of these functions. However, we know now that KCs are not the only macrophage population in the liver, that recently was shown to contain also capsular macrophages, monocyte-derived macrophages as well as recruited peritoneal macrophages inherited from previous inflammatory events. These macrophages exhibit different origins, time of establishing residence and locations in the liver, with both ontogenical and environmental factors shaping their identity and functions. Furthermore, liver macrophages reside in a complex environment with a pronounced metabolic zonation. Here, we briefly discuss how these intrinsic and extrinsic factors influence macrophage biology and liver physiology in general. We notably focus on how the recent advances of single cell transcriptomic approaches are changing our understanding of liver macrophages and diseases.

Keywords: heterogeneity; liver; macrophage; monocyte; single cell RNA sequencing.

Figure 1

Liver macrophage heterogeneity. The liver is populated by different macrophage populations. The most abundant one is composed by embryonically-derived Kupffer cells (KC) which reside in liver sinusoids and interact mainly with HSC and EC. Monocyte-derived macrophages (MoM) can also acquire a KC-like phenotype after inflammation. Liver capsular macrophages (LCM) are present at the level of the liver capsule (LC). Finally, mature peritoneal macrophages (PMs) can also be recruited in the liver notably in case of injuries in the parenchyma. (Neu, Neutrophils).