基于STAT3调控的Th17/Treg免疫失衡在牙周炎所致认知损害中的作用探究

牙周感染及宿主免疫炎症反应是系统性疾病的重要危险因素。以影响认知功能为主的阿尔茨海默病(AD)成为老龄化社会的难题。临床研究显示牙周炎和AD相关，但细胞免疫在二者关联中的作用鲜见报道。信号传导和转录激活因子3(STAT3)是炎症免疫调节中重要的信号转导和转录因子。前期发现牙周炎鼠认知下降，外周和脑STAT3高表达，Th17及相关因子增加而Treg减少，STAT3抑制剂可逆转，初步提示STAT3调节Th17/Treg在牙周炎所致认知损害中发挥作用。本研究拟用多种牙周炎模型和Stat3基因条件性敲除小鼠，从整体、组织、细胞上探究牙周炎致病因子对STAT3介导的Th17和Treg细胞分化及认知功能的影响与机制。以阐明基于STAT3调控的Th17/Treg免疫失衡在牙周炎与认知损害关联机制中的作用，揭示细胞免疫是连接牙周炎和认知损害的桥梁，为探寻牙周干预策略延缓AD发生发展提供实验依据和理论支持。

Periodontitis is a chronic infectious disease caused by plaque microorganisms which leads to the damage of periodontal support tissues. Recurrent periodontal infection and host inflammatory immune responses not only lead to the destruction of periodontal tissues, but also become potential aetiological factors of systemic diseases. With the aging tendency of population, the impact of Alzheimer's Disease(AD), characterized by progressive impairment of numerous cognitive domains, on public health resources will be significant.. Clinical studies have shown close association between periodontitis and AD. However, there is insufficient report on the cell-mediated immunity mechanisms between periodontitis and cognitive impairment. The transcriptional regulator STAT3, a member of the STAT (signal transducers and activators of transcription) family, has key roles in the control of immunity and inflammation. In our previous studies, periodontitis induced by periodontal ligation or the administration of Porphyromonas gingivalis lipopolysaccharide could impair the ability of learning and memory and trigger peripheral and central inflammation. Moreover, the STAT3 pathway was activated. Th17 cells and related pro-inflammatory cytokines were increased while Treg cells and related anti-inflammatory cytokines were decreased in the peripheral tissue and the brain. Furthermore, administration of STAT3 inhibitor could reverse these changes. These results preliminarily indicated that STAT3 could play an important role in cognitive impairment caused by periodontitis via regulating Th17/Treg balance. . The present study is to make use of the different periodontitis animal models and Stat3 conditional knockout mice model to systematically investigate the immunomodulatory effect of STAT3 on the differentiation of Th17 and Treg, and relative immune effection on periodontitis-associated cognitive impairment from the perspectives of the general systems, tissues and cells. Our study will clarify the role of Th17/Treg immune regulation in the correlation mechanism between periodontitis and cognitive impairment. It will reveal that immune regulation could both affect the pathological process of periodontitis and play an important role in cognition. It will be helpful to widen the understanding on the pathology of periodontitis and AD. In the meantime, it will also provide experimental basis and theoretical support on exploring periodontal intervention strategies to delay the occurrence and development of AD.