Immune cell C/EBPβ deficiency is associated with hepatic mononuclear defects and spontaneous hepatitis but not steatohepatitis induced liver fibrosis

免疫细胞 C/EBPβ 缺乏与肝单核细胞缺陷和自发性肝炎有关,但与脂肪性肝炎引起的肝纤维化无关

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作者:Itay Moshkovits, Ayelet Kaminitz, Debby Reuveni, Metsada Pasmanik-Chor, Eli Brazowski, Alexander Mildner, Achim Leutz, Ehud Zigmond

Background

CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor known to be involved in macrophage differentiation and function, steatohepatitis and liver fibrosis.

Conclusions

Immune-restricted C/EBPβ deficiency leads to significant alteration in hepatic mononuclear phagocytes composition associated with spontaneous mild hepatitis. Steatohepatitis associated fibrosis is not dependent on C/EBPβ expression by immune cells.

Methods

Immune restricted C/EBPβ deficient and control mice were investigated in steady-state and in the CDA-HFD steatohepatitis model. Mice were assessed for weight change, liver biochemical profile, histology and hepatic phagocytes composition.

Results

Flow cytometry analysis of hepatic nonparenchymal cells revealed reduced numbers of hepatic monocytes and Kupffer cells and an increase in hepatic MHC class II positive myeloid cells in immune cells restricted C/EBPβ deficient mice. Immune-restricted C/EBPβ deficiency resulted in decreased weight gain and appearance of mild spontaneous liver inflammation. Nevertheless, In the CDA-HFD steatohepatitis model, immune restricted C/EBPβ deficient and proficient mice exhibit similar grade of hepatic steatosis, liver enzymes levels and fibrosis stage. Conclusions: Immune-restricted C/EBPβ deficiency leads to significant alteration in hepatic mononuclear phagocytes composition associated with spontaneous mild hepatitis. Steatohepatitis associated fibrosis is not dependent on C/EBPβ expression by immune cells.

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