Dietary n-3 PUFA Protects Mice from Con A Induced Liver Injury by Modulating Regulatory T Cells and PPAR-γ Expression.
Dietary n-3 PUFA Protects Mice from Con A Induced Liver Injury by Modulating Regulatory T Cells and PPAR-γ Expression.
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膳食 n-3 PUFA 通过调节调节性 T 细胞和 PPAR-γ 表达来保护小鼠免受 Con A 诱导的肝损伤
DOI：
10.1371/journal.pone.0132741
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hua J
中科院分区：
文献类型：
--
作者：
Lian M;Luo W;Sui Y;Li Z;Hua J
饲粮n-3多不饱和脂肪酸（PUFA）通过下调先天和过继性免疫反应发挥抗炎和免疫调节作用。然而，膳食n-3 PUFA对CD4+CD25+调节性T细胞（Tregs）的影响尚不清楚。目的探讨n-3 PUFA与Tregs的关系及其在免疫介导的肝损伤中的免疫调节作用。方法建立n-3 pufa饲料喂养小鼠模型，分析Tregs。研究了二十二碳六烯酸（DHA）对体外诱导Tregs增殖的影响。通过甲型肝炎模型研究n-3 PUFA的潜在免疫治疗作用。结果长期给予n-3 PUFA可显著增加肝脏Tregs并调节其表型。n-3 PUFA或DHA直接促进天然treg （nTreg）增殖，但对诱导treg （iTreg）增殖无促进作用。此外，n-3 pufa富饲小鼠过氧化物酶体增殖物激活受体γ (PPAR-γ)、转化生长因子β (TGF-β)和白细胞介素-10的表达显著上调。最后，富含n-3 pufa的饮食减轻了Con A诱导的肝损伤，下调了促炎细胞因子的表达，并伴有PPAR-γ的表达升高。结论饲粮n-3 PUFA通过上调PPAR-γ和TGF-β表达促进Tregs的生成，对Con a诱导的小鼠肝损伤具有保护作用。这一发现为治疗炎症性和自身免疫性疾病提供了一种有前景的潜在治疗方法。
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.