Galectin-9/Tim-3 Regulates Macrophage Glycolysis In Peri-Implantitis

To investigate the regulatory role of the Galectin-9/Tim-3 signaling axis in glycolysis and macrophage metabolism during peri-implantitis (PI), and to evaluate the therapeutic potential of exogenous Galectin-9 (Gal-9) in restoring immune homeostasis. Animal Study: Twenty-four rats with titanium implants were divided into three groups after 4 weeks of osseointegration: Control (no treatment), PI model (saline-treated with LPS injection and silk ligature for 6 weeks), and Gal-9-treated PI model. Gingival tissue levels of STAT1 mRNA, lactate, TNF-α mRNA, and IL-1β mRNA were quantified.Cell Study: THP-1-derived macrophages (Mφ) were polarized into M1 phenotype and divided into four groups: Untreated, M1-polarized control, Gal-9-treated, and Tim-3 inhibitor-treated. Cellular expression of STAT1 mRNA, lactate, TNF-α mRNA, and IL-1β mRNA was analyzed. Statistical analysis was performed using SPSS 25.0. 1.In vivo, Gal-9-treated macrophages exhibited reduced expression of these biomarkers versus both M1-polarized controls and Tim-3 inhibitor groups (P<0.05).2.In vitro, Gal-9-treated macrophages exhibited reduced expression of these biomarkers versus both M1-polarized controls and Tim-3 inhibitor groups (P<0.05). Exogenous Gal-9 suppresses STAT1-mediated glycolysis and pro-inflammatory cytokine production via the Galectin-9/Tim-3 axis, suggesting its therapeutic potential in attenuating metabolic reprogramming and immune dysregulation in peri-implantitis. Targeting this pathway may offer novel strategies for PI management.