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

Background: CCAAT/enhancer-binding protein beta (C/EBP beta) is a transcription factor known to be involved in macrophage differentiation and function, steatohepatitis and liver fibrosis. Methods: Immune restricted C/EBP beta 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/EBP beta deficient mice. Immune-restricted C/EBP beta deficiency resulted in decreased weight gain and appearance of mild spontaneous liver inflammation. Nevertheless, In the CDA-HFD steatohepatitis model, immune restricted C/EBP beta deficient and proficient mice exhibit similar grade of hepatic steatosis, liver enzymes levels and fibrosis stage. Conclusions: Immune-restricted C/EBP beta deficiency leads to significant alteration in hepatic mononuclear phagocytes composition associated with spontaneous mild hepatitis. Steatohepatitis associated fibrosis is not dependent on C/EBP beta expression by immune cells.