ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica

Aims: The Schistosoma japonicum (S. japonicum)-infected ApoE gene deficiency (ApoE^-/- ) mice were used to determine effect of ApoE on hepatic immunopathology.

Methods: Murine activities and appetite, body weight, ratio of liver weight to its body weight (Hepatic mass index, HMI) were observed. Worm load and liver egg burden were evaluated as the infection intensity. Number and size of liver egg granulomas and serum levels of alanine aminotransferase (ALT) were investigated. We analyzed hepatic fibrosis by markers of fibrosis in tissue, detected hepatic Th17 and Treg frequency by flow cytometry, measured hepatic expressions of RORγt, Foxp3, IL-17A, and TGF-β1 via qPCR. Lipid metabolism was determined by serum levels of cholesterol (TC) and triglyceride (TG) as well as hepatic Oil red O staining.

Results: In the infected ApoE^-/- mice, the increased infection intensity aggravated the hepatic immunopathology (evidenced by increased HMI, elevated egg granulomas, increased ALT levels) and fibrosis (increased hepatic collagen deposition). ApoE deficiency resulted in significantly elevated ratio of hepatic Th17/Treg and higher serum levels of TC and TG, along with higher level of hepatic Oil red O staining.

Conclusions: ApoE deficiency promotes hepatic pathology and fibrosis by exacerbating Th17/Treg imbalance and altering lipid metabolism in murine schistosomiasis japonica.

Keywords: Schistosoma japonicum; ApoE; Fibrosis; Hepatic pathology; Lipid metabolism; Th17; Treg.