Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct from Kupffer Cells in the Fatty Liver
Anneleen Remmerie, Liesbet Martens, Tinne Thoné, Ângela Castoldi, Ruth Seurinck, Benjamin Pavie, Joris Roels, Bavo Vanneste, Sofie De Prijck, Mathias Vanhockerhout, Mushida Binte Abdul Latib, Lindsey Devisscher, Anne Hoorens, Johnny Bonnardel, Niels Vandamme, Anna Kremer, Peter Borghgraef, Hans Van Vlierberghe, Saskia Lippens, Edward J. Pearce, Yvan Saeys, Charlotte L. Scott
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.