Docosahexaenoic acid prevents dendritic cell maturation, inhibits antigen-specific Th1/Th17 differentiation and suppresses experimental autoimmune encephalomyelitis.
Docosahexaenoic acid prevents dendritic cell maturation, inhibits antigen-specific Th1/Th17 differentiation and suppresses experimental autoimmune encephalomyelitis.
复制标题
DOI：
10.1016/j.bbi.2010.09.012
复制
发表时间：
2011-07
影响因子：
15.1
通讯作者：
Ganea, Doina
中科院分区：
文献类型：
--
作者：
Kong, Weimin;Yen, Jui-Hung;Ganea, Doina
关键词：
二十二碳六烯酸（DHA）是中枢神经系统中含量最丰富的必需n-3多不饱和脂肪酸，最近与二十碳五烯酸（EPA）和DHA/EPA代谢衍生物一起出现，作为解决炎症的主要参与者。在结肠炎、败血症和中风的临床研究和动物模型中报告了DHA的保护性抗炎作用。在这里，我们报告的第一次饮食n-3脂肪酸在实验性自身免疫性脑脊髓炎（EAE），人类多发性硬化症模型的有益效果。在本研究中，我们研究了DHA对骨髓来源的树突状细胞（DC）在CD 4 + T细胞刺激和分化中的功能的影响。用DHA预处理DC阻止LPS诱导的DC成熟，维持以共刺激分子低表达和缺乏促炎细胞因子（IL-12 p70、IL-6和IL-23）产生为特征的不成熟表型。DHA处理的DC在增殖和Th 1/Th 17分化方面是抗原特异性T细胞的不良刺激物。这与细胞周期阻滞剂p27（kip 1）的增加以及Th 1、Th 2和Th 17的主要转录因子Tbet、加塔-3和RORγt的减少有关。相反，与DC-DHA共培养的T细胞表达更高水平的TGFβ和Foxp 3，而不表现出功能性Treg表型。与体外结果相似，DHA在EAE中的有益作用与脾脏和CNS中产生IFNγ和IL-17的CD 4 + T细胞数量减少有关。
Docosahexaenoic acid (DHA), the most abundant essential n-3 polyunsaturated fatty acid in the CNS, emerged recently together with eicosapentaenoic acid (EPA) and DHA/EPA metabolic derivatives as a major player in the resolution of inflammation. Protective antiinflammatory effects of DHA were reported in clinical studies and animal models of colitis, sepsis, and stroke. Here we report for the first time a beneficial effect of dietary n-3 fatty acids in experimental autoimmune encephalomyelitis (EAE), a model for human multiple sclerosis. In the present study we investigated the effects of DHA on the function of bone marrow-derived dendritic cells (DC) in CD4+ T cell stimulation and differentiation. Pretreatment of DC with DHA prevented LPS-induced DC maturation, maintaining an immature phenotype characterized by low expression of costimulatory molecules and lack of proinflammatory cytokine production (IL-12p70, IL-6 and IL-23). DHA-treated DC were poor stimulators of antigen-specific T cells in terms of proliferation and Th1/Th17 differentiation. This was associated with an increase in p27(kip1), a cell cycle arresting agent, and with decreases in Tbet, GATA-3 and RORγt, master transcription factors for Th1, Th2, and Th17. In contrast, T cells co-cultured with DC-DHA express higher levels of TGFβ and Foxp3, without exhibiting a functional Treg phenotype. Similar to the in vitro results, the beneficial effect of DHA in EAE was associated with reduced numbers of IFNγ- and IL-17-producing CD4+ T cells in both spleen and CNS.
登录
查看更多内容
DOI：
10.1016/j.plefa.2009.05.010
发表时间：
2009-08
期刊：
Prostaglandins, leukotrienes, and essential fatty acids
影响因子：
--
作者：
Chapkin RS;Kim W;Lupton JR;McMurray DN
通讯作者：
McMurray DN
影响因子：
4.2
作者：
Beli, Eleni;Li, Maoxiang;Pestka, James J.
通讯作者：
Pestka, James J.
影响因子：
4.4
作者：
Hasturk, Hatice;Kantarci, Alpdogan;Van Dyke, Thomas E.
通讯作者：
Van Dyke, Thomas E.
DOI：
10.1086/650344
发表时间：
2010-02-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Bonilla DL;Fan YY;Chapkin RS;McMurray DN
通讯作者：
McMurray DN
影响因子：
16.2
作者：
Calon, F;Lim, GP;Cole, GM
通讯作者：
Cole, GM