CD4+RORγt++ and Tregs in a Mouse Model of Diet-Induced Nonalcoholic Steatohepatitis

الملخص EN

Background and Aims.

Inflammatory mediators that cross-talk in different metabolically active organs are thought to play a crucial role in the pathogenesis of Nonalcoholic Steatohepatitis (NASH).

This study was aimed at investigating the CD4+RORγt+ T-helper cells and their counterpart, the CD4+CD25+FOXP3+ regulatory T cells in the liver, subcutaneous adipose tissue (SAT), and abdominal adipose tissue (AAT) in a high fat diet (HFD) mouse model.

Methods.

C57BL6 mice were fed a HFD or a normal diet (ND).

Liver enzymes, metabolic parameters, and liver histology were assessed.

The expression of CD4+RORγt+ cells and regulatory T cells in different organs (blood, liver, AAT, and SAT) were analyzed by flow cytometry.

Cytokine and adipokine tissue expression were studied by RT-PCR.

Results.

Mice fed a HFD developed NASH and metabolic alterations compared to normal diet.

CD4+RORγt++ cells were significantly increased in the liver and the AAT while an increase of regulatory T cells was observed in the SAT of mice fed HFD compared to ND.

Inflammatory cytokines were also upregulated.

Conclusions.

CD4+RORγt++ cells and regulatory T cells are altered in NASH with a site-specific pattern and correlate with the severity of the disease.

These site-specific differences are associated with increased cytokine expression.