ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Inflammation Pharmacology
This article is part of the Research TopicDecoding Immune Heterogeneity: Therapeutic Responses and Resistance in Diverse Cellular LandscapesView all 11 articles
A thermosensitive hydrogel encapsulating 2-DG alleviates periodontitis by inhibiting glycolysis and effector response of Th17 cells
Provisionally accepted
- 1Shanghai Engineering Research Center of Tooth Restoration and Regeneration, The Affiliated Stomatology Hospital, Tongji University, Shanghai, China
- 2Tongji University Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China
- 3Julius-Maximilians-Universitat Wurzburg, Würzburg, Germany
- 4Fudan University Institutes of Biomedical Sciences, Shanghai, China
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Objective: To investigate the mechanism of Th17 cells in immunomodulation during periodontitis and develop a localized drug delivery system based on glycolysis inhibition for safer and more effective therapeutic interventions. Methods: Periodontitis models were established via the use of IL17A-KO mice to evaluate the impact of Th17-related cytokine deficiency on pathological progression. Using single-cell RNA sequencing (scRNA-seq), we investigated the metabolic profile of CD4+ T cells under periodontitis conditions. The glycolysis inhibitor 2-deoxy-D-glucose (2-DG) was used to assess its ability to suppress CD4+ T-cell proliferation and Th17 differentiation. A thermosensitive PLGA-PEG-PLGA hydrogel encapsulating 2-DG was synthesized and locally administered to a murine periodontitis model. Results: IL17A-KO mice exhibited significantly attenuated alveolar bone resorption. Single-cell RNA sequencing revealed that, under periodontitis conditions, CD4+ T cells exhibited enhanced differentiation toward Th17 cells and increased glycolysis. The 2-DG hydrogel inhibited CD4+ T-cell expansion and Th17 polarization. Local application of the 2-DG hydrogel reduced periodontal inflammation, decreased bone destruction, and diminished granulocyte infiltration in gingival tissues. Conclusion: Th17-cell differentiation exacerbates periodontitis progression, and glycolysis inhibition effectively modulates Th17-driven immunity. The localized 2-DG hydrogel delivery system presents a promising translational strategy for periodontitis management.
Keywords: 2-DG, Hydrogel, Metabolism, Periodontitis, Th17 Cells
Received: 15 Dec 2025; Accepted: 03 Feb 2026.
Copyright: © 2026 Zhao, Li, Yin, Xu, Chen, Yan, Chen, Fu and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jiayao Fu
Junhua Wu
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