FBS Colloquia No.372Laboratory of Immunology and Cell Biology

A periportal macrophage subset protects the host liver from commensal-driven inflammation

The liver is organized into two main zones, portal vein (PV) and central vein (CV) zones. PV zone is the gateway from the gut, and constantly receives gut bacteria or related substances. Although PV zone is always under inflammatory loads, the liver tissue keeps homeostasis without excessive inflammation. Our multimodal spatial analyses using intravital imaging and spatial transcriptomics revealed periportal localization of an immunosuppressive macrophage (Kupffer cell) subset highly expressing an anti-inflammatory cytokine interleukin-10 (IL-10) and a scavenger receptor Marco. This subset phagocytizes more amount of dead cells and/or bacteria while producing IL-10, consequently suppressing inflammatory responses.

Next, we examined physiological importance of this subset by inducing intestinal barrier disruption and promoting bacterial translocation into the liver. In this experiment, we compared wild-type control mice to knockout mice with dysfunctional target macrophages. Infiltration of inflammatory cells including neutrophils and T cells, liver damage, and fibrosis were augmented in the knockout mice, suggesting that the immunosuppressive macrophage subset protects the liver from gut bacteria-driven inflammatory disorder.