title: Dietary n-3 PUFA Protects Mice from Con A Induced Liver Injury by Modulating Regulatory T Cells and PPAR-γ Expression.
abstract: BACKGROUND
  Dietary n-3 polyunsaturated fatty acids (PUFA) exert anti-inflammatory and immunoregulatory effects through down-regulating the innate and adoptive immune response. However, the effect of dietary n-3 PUFA on CD4+CD25+ regulatory T cells (Tregs) is unclear.
  
  
  OBJECTIVE
  The current study was to examine the relationship between n-3 PUFA and Tregs as well as their immunoregulatory effect in immune-mediated liver injury.
  
  
  METHODS
  The mice model feeding with n-3 PUFA-enriched diet was established and Tregs were analyzed. Effect of docosahexaenoic acid (DHA) on Tregs proliferation and induction was determined in vitro. The potential immunotherapeutic effect of dietary n-3 PUFA was investigated through Con A-induced hepatitis model.
  
  
  RESULTS
  Long-term administration of dietary n-3 PUFA significantly increased hepatic Tregs and modulated their phenotype. n-3 PUFA or DHA directly increased natural Tregs (nTreg) proliferation but didn't increase inducible Tregs (iTreg). In addition, the expression of peroxisome proliferator activated receptor gamma (PPAR-γ), transforming growth factor β (TGF-β) and interleukin (IL)-10 were significantly up-regulated in n-3 PUFA-enriched diet-fed mice. Finally, n-3 PUFA-enriched diet alleviated liver injury induced by Con A and down-regulated pro-inflammatory cytokines expression, accompanied by increased PPAR-γ expression.
  
  
  CONCLUSIONS
  Dietary n-3 PUFA enhanced Tregs generation through up-regulating PPAR-γ and TGF-β expression, and protected mice from Con A-induced liver injury. This finding provides a promising potential therapeutic method in treating inflammatory and autoimmune disease.
authors.affiliation: Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Lian
authors.affiliation: Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Luo
authors.affiliation: Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, P.R. China.
authors.forename: Yongheng
authors.initials: Y
authors.lastname: Sui
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hua
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D003208:Concanavalin A; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D047495:PPAR gamma; D003208:Concanavalin A