Mucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Mucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Immunity. 2019 Oct 15;51(4):671-681.e5. doi: 10.1016/j.immuni.2019.08.001. Epub 2019 Aug 23.
Diet has been suggested to be a potential environmental risk factor for the increasing incidence of autoimmune diseases, yet the underlying mechanisms remain elusive. Here, we show that high glucose intake exacerbated autoimmunity in mouse models of colitis and experimental autoimmune encephalomyelitis (EAE). We elucidated that high amounts of glucose specifically promoted T helper-17 (Th17) cell differentiation by activating transforming growth factor-β (TGF-β) from its latent form through upregulation of reactive oxygen species (ROS) in T cells. We further determined that mitochondrial ROS (mtROS) are key for high glucose-induced TGF-β activation and Th17 cell generation. We have thus revealed a previously unrecognized mechanism underlying the adverse effects of high glucose intake in the pathogenesis of autoimmunity and inflammation.
饮食被认为是导致自身免疫性疾病发病率上升的一个潜在环境风险因素，但潜在机制仍难以捉摸。在这里，我们表明，高糖摄入加剧了结肠炎和实验性自身免疫性脑脊髓炎（EAE）小鼠模型中的自身免疫。我们阐明，高浓度的葡萄糖通过上调 T 细胞中的活性氧（ROS），特异性地从潜伏形式激活转化生长因子-β（TGF-β），从而促进辅助性 T 细胞 17（Th17）细胞分化。我们进一步确定，线粒体 ROS（mtROS）是高糖诱导的 TGF-β激活和 Th17 细胞生成的关键。因此，我们揭示了高糖摄入在自身免疫和炎症发病机制中产生不良影响的一个以前未被认识的机制。
