Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct from Kupffer Cells in the Fatty Liver

Immunity. 2020 Sep 15;53(3):641-657.e14. doi: 10.1016/j.immuni.2020.08.004. Epub 2020 Sep 3.


Metabolic-associated fatty liver disease (MAFLD) represents a spectrum of disease states ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs), are suggested to play important roles in the pathogenesis of MAFLD through their activation, although the exact roles played by these cells remain unclear. Here, we demonstrated that KCs were reduced in MAFLD being replaced by macrophages originating from the bone marrow. Recruited macrophages existed in two subsets with distinct activation states, either closely resembling homeostatic KCs or lipid-associated macrophages (LAMs) from obese adipose tissue. Hepatic LAMs expressed Osteopontin, a biomarker for patients with NASH, linked with the development of fibrosis. Fitting with this, LAMs were found in regions of the liver with reduced numbers of KCs, characterized by increased Desmin expression. Together, our data highlight considerable heterogeneity within the macrophage pool and suggest a need for more specific macrophage targeting strategies in MAFLD.

Keywords: Kupffer cells; MAFLD; NAFLD; NASH; Western Diet; lipid; liver; macrophages; subsets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Bone Marrow Cells / cytology*
  • Cells, Cultured
  • Desmin / metabolism
  • Female
  • Kupffer Cells / cytology
  • Liver / pathology
  • Macrophage Activation / immunology*
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Osteopontin / metabolism*
  • Proteome / metabolism
  • Transcriptome / genetics


  • Biomarkers
  • Desmin
  • Proteome
  • Osteopontin