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Updated: Jan 18, 2026
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
Stat3-mediated Th17 pathogenicity induced by periodontitis contributes to cognitive impairment by promoting
Yining Zhou1,2,3,4,5, Xinyi Xie1,2,3,4,5,6, Huiwen Chen1,2,3,4,5
1Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Introduction:
Periodontitis has been identified as a potential risk factor for cognitive impairment associated with immune dysregulation. T helper 17 (Th17) cell-associated immune responses are involved in both diseases, while signal transducer and activator of transcription 3 (Stat3) is kown to be crucial for Th17 pathogenicity. Accordingly, in this study, we investigated how Stat3-mediated Th17 pathogenicity contributes to the link between periodontitis and cognitive impairment.
Methods:
Levels of Th17-related cytokines in gingival crevicular fluid (GCF) were measured in individuals with and without cognitive impairment. A periodontitis model was established in mice with conditional deletion of Stat3 in Th17 cells (Stat3 fl/fl; Il17a-CreERT2, cKO) and wild type (Stat3 fl/fl, WT) mice via injection of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) into gingival sulcus. Cognitive function was assessed through behavioral tests. Expression of Th17-related cytokines and microglial pro-inflammatory markers was evaluated by reverse transcription-quantitative PCR (RT-qPCR), ELISA, flow cytometry, and immunohistochemistry. To evaluate effects of CD4+ T cells on microglial M1 polarization, BV2 microglia were co-cultured with primary CD4+T cells which were stimulated with P. gingivalis LPS after isolated from cKO and WT mice.
Results:
Compared with cognitively normal participants, levels of Th17-related cytokines increased in participants with cognitive impairment. Significant alveolar bone resorption and cognitive impairment were observed in WT mice with periodontitis. These periodontitis-induced changes were alleviated in cKO mice, accompanied by a weakening of neuroinflammation and mitigation of Th17 immune responses. In vitro, M1 polarization and activation of the MAPK/ERK signaling pathway were inhibited in BV2 cells co-cultured with Stat3-deleted Th17 cells.
Conclusion:
Stat3-mediated Th17 pathogenicity bridged the correlation between periodontitis and neuroinflammation related to cognitive impairment, offering novel perspectives for a therapeutic target for blocking the mouth-to-brain axis.
