title: CD4+ROR γ t++ and Tregs in a Mouse Model of Diet-Induced Nonalcoholic Steatohepatitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2560 Antwerp, Belgium ; Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, 70100 Bari, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Vonghia
authors.affiliation: Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, 2560 Antwerp, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ruyssers
authors.affiliation: Laboratory of Pharmacology, University of Antwerp, 2560 Antwerp, Belgium.
authors.forename: Dorien
authors.initials: D
authors.lastname: Schrijvers
authors.affiliation: Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2560 Antwerp, Belgium ; Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, 2560 Antwerp, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Pelckmans
authors.affiliation: Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2560 Antwerp, Belgium ; Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, 2560 Antwerp, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Michielsen
authors.affiliation: Laboratory of Immunology, Allergology and Rheumatology, University of Antwerp, 2560 Antwerp, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: De Clerck
authors.affiliation: Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2560 Antwerp, Belgium ; International Tissue Engineering Research Association (ITERA) Life Sciences Forum, 3620 Lanaken, Belgium ; Genetisch-Diagnostisches Labor, 50939 Köln, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Ramon
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, 70100 Bari, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Jirillo
authors.affiliation: Laboratory of Immunology, Allergology and Rheumatology, University of Antwerp, 2560 Antwerp, Belgium.
authors.forename: Didier
authors.initials: D
authors.lastname: Ebo
authors.affiliation: Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, 2560 Antwerp, Belgium.
authors.forename: Benedicte
authors.initials: B
authors.lastname: De Winter
authors.affiliation: Laboratory of Immunology, Allergology and Rheumatology, University of Antwerp, 2560 Antwerp, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Bridts
authors.affiliation: Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2560 Antwerp, Belgium ; Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, 2560 Antwerp, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Francque
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3