miR-181a调控Th17/Treg细胞免疫在阿尔茨海默病（AD）中的作用及机制研究

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. But so far there is no specific therapy for it. Recently immunization has been widely concerned in the diagnosis and treatment of AD.The immune inflammation mediated by T cells play an important role in the development of Alzheimer's disease. Th17/Treg cell may be one of the key regulators, and the changes of Th17 /Treg cell subsets may be involved in the pathophysiological process of AD. miRNA181a was abundantly expressed in the brain and was one of the most important miRNA which regulating T cell immunization. miR-181a also involved in the development , maturation, differentiation and balance of T lymphocytes, especially Th17 cell and Treg cell.These involved in the pathophysiological process of AD has not been reported. Therefore, this study suggest that, in the development of AD,miR-181a maybe alter Th17/Treg through PTEN mediated PI13k/AKT signaling pathway.

阿尔茨海默病（Alzheimer’s disease，AD）是老年痴呆最常见的原因，免疫调节策略在AD的诊治过程中近来受到广泛关注，T细胞介导的免疫炎症在AD的发生和发展过程中具有重要作用，Th17/Treg介导的免疫稳态可能是AD病发展过程的关键调节因子之一，其作用贯穿于AD的发病过程中。miRNA181a是调控T细胞免疫的重要miRNA之一，miRNA181a在脑内表达丰富，抑制miR-181a可减轻神经元丢失，同时miR-181a参与T淋巴细胞的发育、成熟、分化过程。对于miR-181a是否能够通过调控T细胞亚群分化与成熟，尤其T h17/Treg，参与AD的早期病理生理过程尚未见报道。本课题探讨miR-181a是否通过调控Th17、Treg细胞的分化和成熟，调节Th17/Treg细胞免疫平衡，参与AD的发生发展。其主要调节途径可能与PTEN介导的PI3K／AKT信号通路有关。

阿尔茨海默病（Alzheimer’s disease，AD）是老年痴呆最常见的原因，已证实神经免疫炎症参与AD发病过程中，AD的神经免疫学机制复杂，辅助性T细胞17（Th17）和调节性T细胞（Treg）细胞通过细胞因子间的相互作用、转换及两者免疫稳态失衡等参与AD的发病过程。miRNA181a参与T淋巴细胞的发育、成熟、分化过程。我们的研究发现与认知正常人群相比，AD患者外周血miR181a表达增加，Th17细胞比率上升，Treg细胞及淋巴细胞亚群在各人群中变化不大，而Th17/Treg比值在AD人群中显著升高，炎症因子IL-4、IL-6、IL-17A、IL-10、r-IFN水平也显著升高，线性相关性分析发现外周miR181a与Th17/Treg成正相关。为进一步验证miR181a在AD中的作用，在APP/PS1转基因小鼠生长期内3个月、6个月、9个月、12个月提取外周血及脑组织，检测Th17、Treg、Th17/Treg及miR-181a1的表达水平，并使用Morris水迷宫检测小鼠认知功能。结果发现APP/PS1小鼠从6月龄开始血中和海马中miR181a1表达上调，同时伴随者Th17/treg失衡。抑制miR181a1表达可改善APP/PS1小鼠认知功能，miR181a1表达下调后Th17/Treg比值也进一步下降，提示miR181a1过表达参与AD的发病中，作用机制可能与Th17/Treg失衡有关，但具体作用机制还需进一步探讨。