Open AccessImmune cell C/EBPβ deficiency is associated with hepatic mononuclear defects and spontaneous hepatitis but not steatohepatitis induced liver fibrosis
Author(s) -
Moshkovits Itay,
Kaminitz Ayelet,
Reuveni Debby,
PasmanikChor Metsada,
Brazowski Eli,
Mildner Alexander,
Leutz Achim,
Zigmond Ehud
Publication year - 2022
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.728
Subject(s) - steatohepatitis , immune system , steatosis , fibrosis , hepatic stellate cell , hepatic fibrosis , inflammation , biology , medicine , endocrinology , immunology , fatty liver , disease
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. 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.