Periodontitis is one of the most common oral diseases worldwide, and it is associated with various systemic diseases, including cognitive diseases. STAT3 regulates the inflammatory cascade and influences adaptive immunity by modulating Th17/Treg cell differentiation. In this study, we aimed to explore the effect of adaptive immunity inside and outside the brain on the association between periodontitis and cognitive impairment and understand the role of the STAT3 signaling pathway. We established Porphyromonas gingivalis LPS-induced periodontitis mice models by injecting P. gingivalis LPS into the gingival sulcus of mice. Behavioral tests showed that learning and memory abilities were impaired. The flow cytometry data showed an imbalance in the Th17/Treg ratio in the blood and brain samples of the mice. The expression of Th17-related cytokines (IL-1β, IL-17A, IL-21, and IL-22) increased, whereas that of Treg-related cytokines (IL-2 and IL-10) decreased in both the blood and the brain. The level of LPS increased and the STAT3 signaling pathway was activated during this process. These effects were reversed by C188-9, a STAT3 inhibitor. In conclusion, P. gingivalis LPS-induced periodontitis may promote the occurrence and progression of cognitive impairment by modulating the Th17/Treg balance inside and outside the brain. The STAT3 signaling pathway may have immunoregulatory effects on the mouth-to-brain axis.

中文翻译：

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Th17/Treg 失衡通过 STAT3 激活调节 P. gingivalis LPS 诱导的牙周炎小鼠的认知障碍

牙周炎是世界范围内最常见的口腔疾病之一，它与多种全身性疾病有关，包括认知疾病。STAT3 通过调节 Th17/Treg 细胞分化来调节炎症级联反应并影响适应性免疫。在本研究中，我们旨在探讨大脑内外适应性免疫对牙周炎与认知障碍之间关联的影响，并了解 STAT3 信号通路的作用。我们通过注射牙龈卟啉单胞菌建立牙龈卟啉单胞菌LPS诱导的牙周炎小鼠模型LPS 进入小鼠牙龈沟。行为测试表明学习和记忆能力受损。流式细胞术数据显示小鼠血液和脑样本中 Th17/Treg 比率不平衡。Th17 相关细胞因子（IL-1β、IL-17A、IL-21 和 IL-22）的表达增加，而 Treg 相关细胞因子（IL-2 和 IL-10）的表达在血液和脑。在此过程中，LPS 水平升高，STAT3 信号通路被激活。这些作用被 STAT3 抑制剂 C188-9 逆转。总之，P. gingivalisLPS 诱导的牙周炎可能通过调节脑内外的 Th17/Treg 平衡来促进认知障碍的发生和进展。STAT3 信号通路可能对口脑轴具有免疫调节作用。