Accumulated myeloid-derived suppressor cells demonstrate distinct phenotypes and functions in two non-alcoholic steatohepatitis mouse models

Background: To examine the steady state of hepatic myeloid-derived suppressor cells (MDSCs) and thelipid accumulation and inflammation-related changes in these cells, we analyzed the presence and functionsof hepatic MDSCs in the following two non-alcoholic steatohepatitis (NASH) mouse models.Methods: Monosodium glutamate (MSG) model; MSG was subcutaneously injected into neonatal maleC57BL/6J mice that were fed with normal diet up to 18 weeks of age. Methionine/choline-deficient diet(MCD) model; 16-week-old male C57BL/6J mice were fed with an MCD for 2 weeks. Those hepaticMDSCs were evaluated by flow cytometry and immunohistochemically.Results: Both MSG and MCD mice exhibited greater numbers of hepatic lipid droplets than 18-week-oldmale control mice. Hepatocellular ballooning was obvious in MSG, whereas inflammatory cell infiltrationwere apparent in MCD mice. CD11b, CD115, and Gr-1-positive hepatic MDSCs were increased in bothmodels but higher in MCD mice, and demonstrated higher expression of an M2 macrophage markerCD206 mean fluorescence intensity (MFI) in MSG compared to MCD mice. Degree of reactive oxygenspecies production was evaluated using the DCFDA MFI values, which were significantly elevated in hepaticMDSCs from MCD mice. MSG mouse livers demonstrated Gr-1 positive cell accumulation around lipiddroplets, mimicking crown-like structures in adipose tissues. In contrast, hepatic Gr-1 positive cells wereprimarily located in inflammatory cell aggregates in MCD mice.Conclusions: These results suggest that hepatic fatty changes promote MDSC accumulation, andinflammatory changes induce phenotypic and functional alteration in hepatic MDSCs in NASH mousemodels.