Abstract
BackgroundDietary 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.AimsThe current study was to examine the relationship between n-3 PUFA and Tregs as well as their immunoregulatory effect in immune-mediated liver injury.MethodsThe 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.ResultsLong-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.ConclusionDietary 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.
Highlights
Dietary n-3 polyunsaturated fatty acids (n-3 PUFA) possess significant immunosuppressive and anti-inflammatory properties, they exert beneficial effects with respect to some inflammatory diseases and immune-mediated diseases [1,2,3,4]
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
PPAR-γ, a member of the nuclear receptors and a ligand-dependent transcription factor, can regulate insulin and glucose metabolism, and has the ability to down-regulate the immune response of cells in the innate and adaptive immune system [5,6]
Summary
Dietary n-3 polyunsaturated fatty acids (n-3 PUFA) possess significant immunosuppressive and anti-inflammatory properties, they exert beneficial effects with respect to some inflammatory diseases and immune-mediated diseases [1,2,3,4]. PPAR-γ, a member of the nuclear receptors and a ligand-dependent transcription factor, can regulate insulin and glucose metabolism, and has the ability to down-regulate the immune response of cells in the innate and adaptive immune system [5,6]. CD4+CD25+ regulatory T cells (Tregs) play a critical role in maintaining peripheral self-tolerance and controlling pathogenic-specific responses. Dietary n-3 polyunsaturated fatty acids (PUFA) exert anti-inflammatory and immunoregulatory effects through down-regulating the innate and adoptive immune response. The effect of dietary n-3 PUFA on CD4+CD25+ regulatory T cells (Tregs) is unclear
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