title: Accumulated myeloid-derived suppressor cells demonstrate distinct phenotypes and functions in two non-alcoholic steatohepatitis mouse models.
abstract: BACKGROUND
  To examine the steady state of hepatic myeloid-derived suppressor cells (MDSCs) and the lipid accumulation and inflammation-related changes in these cells, we analyzed the presence and functions of hepatic MDSCs in the following two non-alcoholic steatohepatitis (NASH) mouse models.
  
  
  METHODS
  Monosodium glutamate (MSG) model; MSG was subcutaneously injected into neonatal male C57BL/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 hepatic MDSCs were evaluated by flow cytometry and immunohistochemically.
  
  
  RESULTS
  Both MSG and MCD mice exhibited greater numbers of hepatic lipid droplets than 18-week-old male control mice. Hepatocellular ballooning was obvious in MSG, whereas inflammatory cell infiltration were apparent in MCD mice. CD11b, CD115, and Gr-1-positive hepatic MDSCs were increased in both models but higher in MCD mice, and demonstrated higher expression of an M2 macrophage marker CD206 mean fluorescence intensity (MFI) in MSG compared to MCD mice. Degree of reactive oxygen species production was evaluated using the DCFDA MFI values, which were significantly elevated in hepatic MDSCs from MCD mice. MSG mouse livers demonstrated Gr-1 positive cell accumulation around lipid droplets, mimicking crown-like structures in adipose tissues. In contrast, hepatic Gr-1 positive cells were primarily located in inflammatory cell aggregates in MCD mice.
  
  
  CONCLUSIONS
  These results suggest that hepatic fatty changes promote MDSC accumulation, and inflammatory changes induce phenotypic and functional alteration in hepatic MDSCs in NASH mouse models.
authors.affiliation: 1 Fourth Department of Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki-shi, Kanagawa 213-8507, Japan ; 2 Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama-shi, Toyama 930-0194, Japan ; 3 Department of General Medical Practice and Laboratory Diagnostic Medicine, Akita University Graduate School of Medicine, Akita-shi, Akita 010-8543, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Tsunashima
authors.affiliation: 1 Fourth Department of Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki-shi, Kanagawa 213-8507, Japan ; 2 Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama-shi, Toyama 930-0194, Japan ; 3 Department of General Medical Practice and Laboratory Diagnostic Medicine, Akita University Graduate School of Medicine, Akita-shi, Akita 010-8543, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.affiliation: 1 Fourth Department of Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki-shi, Kanagawa 213-8507, Japan ; 2 Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama-shi, Toyama 930-0194, Japan ; 3 Department of General Medical Practice and Laboratory Diagnostic Medicine, Akita University Graduate School of Medicine, Akita-shi, Akita 010-8543, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritoki
authors.affiliation: 1 Fourth Department of Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki-shi, Kanagawa 213-8507, Japan ; 2 Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama-shi, Toyama 930-0194, Japan ; 3 Department of General Medical Practice and Laboratory Diagnostic Medicine, Akita University Graduate School of Medicine, Akita-shi, Akita 010-8543, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Hara
authors.affiliation: 1 Fourth Department of Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki-shi, Kanagawa 213-8507, Japan ; 2 Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama-shi, Toyama 930-0194, Japan ; 3 Department of General Medical Practice and Laboratory Diagnostic Medicine, Akita University Graduate School of Medicine, Akita-shi, Akita 010-8543, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
keywords: Myeloid-derived suppressor cells (MDSCs); non-alcoholic steatohepatitis (NASH)