Intracranial delivery of interleukin-17A via adeno-associated virus fails to induce physical and learning disabilities and neuroinflammation in mice but improves glucose metabolism through AKT signaling pathway.
Intracranial delivery of interleukin-17A via adeno-associated virus fails to induce physical and learning disabilities and neuroinflammation in mice but improves glucose metabolism through AKT signaling pathway.
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DOI：
10.1016/j.bbi.2015.11.005
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Fukuchi KI
中科院分区：
文献类型：
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作者：
Yang J;Kou J;Lim JE;Lalonde R;Fukuchi KI
白细胞介素-17A（IL-17 A）被认为是多发性硬化（MS）的致病因子之一。这方面的间接证据是产生IL-17 A的辅助性T细胞17（Th 17）优先在MS和实验性自身免疫性脑脊髓炎（EAE）的病变中积聚。然而，IL-17 A在MS发病机制中的直接参与仍然是一个悬而未决的问题。在这项研究中，我们通过重组腺相关病毒血清型5（rAAV 5）介导的基因递送在小鼠脑中过表达IL-17 A（IL-17 A-in-Brain小鼠）。尽管IL-17 A在脑和血液中表达水平高，但IL-17 A脑小鼠未表现出炎症反应，运动协调和空间定向也无异常。出乎意料的是，IL-17 A-in-Brain小鼠显示出体重和脂肪组织质量的降低以及葡萄糖耐量和胰岛素敏感性的改善。IL-17 A通过激活AKT增强PC 12细胞中的葡萄糖摄取。我们的研究结果首次提供了直接证据，表明IL-17 A在中枢神经系统中的过表达不会导致身体和学习障碍以及神经炎症，并表明IL-17 A可能通过AKT信号通路调节葡萄糖代谢。
Interleukin-17A (IL-17A) is generally considered as one of the pathogenic factors involved in multiple sclerosis (MS). Indirect evidence for this is that IL-17A-producing T helper 17 (Th17) cells preferentially accumulate in lesions of MS and experimental autoimmune encephalomyelitis (EAE). However, a direct involvement of IL-17A in MS pathogenesis is still an open question. In this study, we overexpressed IL-17A in the brains of mice (IL-17A-in-Brain mice) via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated gene delivery. In spite of high levels of IL-17A expression in the brain and blood, IL-17A-in-Brain mice exhibit no inflammatory responses and no abnormalities in motor coordination and spatial orientation. Unexpectedly, IL-17A-in-Brain mice show decreases in body weight and adipose tissue mass and an improvement in glucose tolerance and insulin sensitivity. IL-17A enhances glucose uptake in PC12 cells by activation of AKT. Our results provide direct evidence for the first time that IL-17A overexpression in the central nervous system does not cause physical and learning disabilities and neuroinflammation and suggest that IL-17A may regulate glucose metabolism through the AKT signaling pathway.