Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine
Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine
复制标题
DOI：
10.1016/j.immuni.2015.09.007
复制
发表时间：
2015-10-20
期刊：
影响因子：
32.4
通讯作者：
Linker, Ralf A.
中科院分区：
文献类型：
--
作者：
Haghikia, Aiden;Joerg, Stefanie;Linker, Ralf A.
越来越多的经验证据表明，营养和细菌代谢物可能会影响疾病和自身免疫背景下的全身免疫反应。我们报道长链脂肪酸 (LCFA) 增强辅助性 T 1 (Th1) 和/或 Th17 细胞的分化和增殖，并通过 p38-MAPK 途径损害其肠道隔离。或者，膳食短链 FA (SCFA) 通过抑制 JNK1 和 p38 通路来扩增肠道 T 调节 (Treg) 细胞。我们使用实验性自身免疫性脑脊髓炎 (EAE) 作为 T 细胞介导的自身免疫模型，表明 LCFA 持续减少肠道中的 SCFA，并通过扩大小肠中的致病性 Th1 和/或 Th17 细胞群而加剧疾病。 SCFA 治疗通过对固有层衍生的 Treg 细胞进行持久印记，改善了 EAE 并减少了轴突损伤。这些数据表明饮食对自身免疫中肠道特异性以及随后中枢神经系统特异性 Th 细胞反应有直接影响，因此可能对多发性硬化症等自身免疫性疾病具有治疗意义。
Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis.