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Journal Article

Osteopontin Expression Identifies a Subsetof Recruited Macrophages Distinctfrom Kupffer Cells in the Fatty Liver

MPS-Authors

Castoldi,  Angela
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce,  Edward J.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Remmerie et al. 2020.pdf
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Citation

Remmerie, A., Martens, L., ́Thone, T., Castoldi, A., Seurinck, R., Pavie, B., et al. (2020). Osteopontin Expression Identifies a Subsetof Recruited Macrophages Distinctfrom Kupffer Cells in the Fatty Liver. Immunity, 53, 641-657. doi:org/10.1016/j.immuni.2020.08.004.


Cite as: http://hdl.handle.net/21.11116/0000-0007-E587-E
Abstract
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.