FBS Colloquia No.286Laboratory of Immunology and Cell Biology

Resident macrophages give rise to spatial heterogeneity of immune responses in the liver.

The liver is organized into two main zones, peri-portal and peri-central zones, each with different concentrations of oxygen and nutrients. Previous studies have indicated that liver-resident cell types, such as hepatocytes, endothelial cells and hepatic stellate cells, exhibit spatially heterogenous functions depending on their zonal location. Particularly, energetically demanding tasks such as continuous production of secreted proteins and metabolic activities are preferentially assigned to the peri-portal zones.
Immune reactions are also energy-consuming processes, but it remains unknown whether spatial compartmentalization of immune systems in the liver exists.
To address this question, in this study, we developed a novel experimental system to spatially analyze immune cell dynamics and comprehensive molecular expression by utilizing intravital two-photon imaging, spatial transcriptome analysis and single-cell transcriptome analysis. As the result, we have unveiled spatial immune regulations in the liver and identified a novel immunoregulatory macrophage subset which asymmetrically localizes within the liver.