Journal Article

Effect of the TIM-3/Gal-9 signaling pathway on macrophage polarization in peri-implantitis

Dong, Shu-Ya, Cheng, Lu-Jin, He, Jun-Gang, Gong, Zhong-Cheng, Mei, Long, Mamat, Aynur, Ni, Xiao-Feng

2025

Overview

Peri-implantitis (PI) is a common complication of oral implant surgeries. Understanding the role of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and its ligand galectin-9 (Gal-9) in PI is essential for advancing treatment strategies. This study investigated the effect of the TIM-3/Gal-9 signaling pathway on macrophage polarization in PI. We included 31 PI patients and 30 controls with healthy implants. Peripheral blood and peri-implant tissue samples were collected. Serum Gal-9 and cytokine levels were measured using ELISA. CD86, CD206, and TIM-3 expressions were analyzed via immunohistochemistry. Lipopolysaccharide was used to induce a PI environment in cells, which were divided into blank control, control, and Gal-9 groups. Flow cytometry detected M1, M2, TIM-3+M1, and TIM-3+M2 proportions. There were positive expressions of CD86 and CD206 in peri-implant tissues of PI patients, indicating the presence of both macrophage phenotypes, with a notable predominance of M1. The proportions of CD86+M1 macrophages and CD206+M2 macrophages in peripheral blood were significantly elevated in the PI group, resulting in an increased M1/M2 ratio in the PI group. Correlation analyses indicated that both M1 and M1/M2 were positively correlated with the modified plaque index, modified sulcular bleeding index, and probing depth, suggesting that the M1/M2 ratio reflects the clinical severity of PI. In vitro experiments showed that the addition of Gal-9 led to a significant increase in the proportion of TIM-3+M1 and TIM-3+M2 macrophages and a decrease in M1 cell proportions and M1/M2 ratio. The Gal-9 group exhibited significantly reduced levels of pro-inflammatory cytokines IL-1β and TNF-α. A strong negative correlation was found between TNF-α levels and TIM-3+M1 macrophages. However, no significant difference was found in the anti-inflammatory cytokine IL-10 between the control and Gal-9 groups. The TIM-3/Gal-9 signaling pathway plays a crucial role in modulating macrophage polarization in PI. This work may provide evidence for the development of novel therapeutic targets for managing PI.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Analysis / Antibodies / B7-2 Antigen - metabolism / Blood / Care and treatment / Case-Control Studies / Causes of / CD86 antigen / Complications and side effects / Correlation analysis / Cytokines / Cytokines - metabolism / Dental prosthetics / Disease prevention / Enzyme-linked immunosorbent assay / Female / Flow cytometry / Galectin-9 / Galectins - blood / Galectins - metabolism / Health aspects / Hepatitis A Virus Cellular Receptor 2 - metabolism / Humans / Immunohistochemistry / Implant dentures / Inflammation / Inflammatory diseases / Lipopolysaccharides / Lymphocytes T / Macrophages / Macrophages - metabolism / Macrophages - pathology / Male / Mannose Receptor / Metabolism / Middle Aged / Mouth diseases / Patients / Peri-Implantitis - metabolism / Peri-Implantitis - pathology / Periodontics / Peripheral blood / Phenotypes / Plaque index / Polarization / Receptors, Cell Surface - metabolism / Signal Transduction / T cells / Therapeutic targets / Transplants & implants / Tumor necrosis factor-TNF / Tumor necrosis factor-α