Effects Of Stat3-Mediated-Th17 On Lps-Induced Neuroinflammation

Periodontitis can induce systemic inflammation and promote development of neuroinflammation. The study investigates how Stat3, as a key transcription factor for Th17 differentiation, participates in the oral-to-brain axis. Mice with specific knockout of Stat3 in Th17 cells (Stat3△Il17a) and wild type mice (WT) were generated and allocated into 4 groups at 8 weeks of age: the WT-NS group, the Stat3△Il17a-NS group, the WT-LPS group and the Stat3△Il17a-LPS group. Mice in the WT-LPS group and the Stat3△Il17a-LPS group were treated with once intraperitoneal injection of 5 mg/kg Escherichia coli-lipopolysaccharide (LPS), whereas the NS groups received an equal volume of saline. 24 hours after injection, open field test (OFT) and elevated zero-maze (EZM) were performed. Neuroinflammation was characterized by immunofluorescence for GFAP and Iba1 in hippocampus. Changes in proportion of Th17 cells were detected via flow cytometry. Experiments were approved (SH9H-2020-A728-1) In OFT and EZM, the WT-LPS group exhibited decreased residence time in the open area, indicating elevated degree of anxiety compared to the WT-NS group. More pronounced neuroinflammation and higher infiltration of Th17 cells in brain tissues of the WT-LPS group were detected than those of the WT-NS group. These sick behaviors and pathological changes were partly alleviated in the Stat3△Il17a-LPS group. LPS-induced neuroinflammation was attenuated by blocking Stat3 and inhibiting Th17 differentiation, highlighting involvement of Stat3-mediated-Th17 pathogenicity in bridging systemic inflammation and neuroinflammation.