{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:35:30Z","timestamp":1791941730179,"version":"4.3.4"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Key Project Funded by the Association for Science and Technology of Autonomous Region","award":["XHXM000319"],"award-info":[{"award-number":["XHXM000319"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec026\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec027\">\n<jats:title>Methods<\/jats:title>\n<jats:p>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<jats:sup>+<\/jats:sup>M1, and TIM-3<jats:sup>+<\/jats:sup>M2 proportions.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec028\">\n<jats:title>Results<\/jats:title>\n<jats:p>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<jats:sup>+<\/jats:sup>M1 macrophages and CD206<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>M1 and TIM-3<jats:sup>+<\/jats:sup>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-1\u03b2 and TNF-\u03b1. A strong negative correlation was found between TNF-\u03b1 levels and TIM-3<jats:sup>+<\/jats:sup>M1 macrophages. However, no significant difference was found in the anti-inflammatory cytokine IL-10 between the control and Gal-9 groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec029\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0328258","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T17:24:20Z","timestamp":1752859460000},"page":"e0328258","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effect of the TIM-3\/Gal-9 signaling pathway on macrophage polarization in 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Alhamad","year":"2023","journal-title":"ACS Appl Bio Mater"},{"issue":"5","key":"pone.0328258.ref005","doi-asserted-by":"crossref","DOI":"10.1563\/aaid-joi-D-14-00068","article-title":"A murine model of lipopolysaccharide-induced peri-implant mucositis and peri-implantitis","volume":"41","author":"FQ Pirih","year":"2015","journal-title":"J Oral Implantol"},{"issue":"3","key":"pone.0328258.ref006","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/clr.13568","article-title":"Characterization of macrophages infiltrating peri-implantitis lesions","volume":"31","author":"T Fretwurst","year":"2020","journal-title":"Clin Oral Implants Res"},{"issue":"2","key":"pone.0328258.ref007","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1189\/jlb.1VMR1216-535R","article-title":"Energy metabolic pathways control the fate and function of myeloid immune cells","volume":"102","author":"AA Al-Khami","year":"2017","journal-title":"J Leukoc 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