Dietary n-3 PUFA Protects Mice from Con A Induced Liver Injury by Modulating Regulatory T Cells and PPAR-γ Expression

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. AIMS: 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. CONCLUSION: 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.