{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:27:44Z","timestamp":1787614064320,"version":"build-2736575974"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:sup>+<\/jats:sup>\n                      T cells under periodontitis conditions. The glycolysis inhibitor 2-deoxy-D-glucose (2-DG) was used to assess its ability to suppress CD4\n                      <jats:sup>+<\/jats:sup>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IL17A-KO mice exhibited significantly attenuated alveolar bone resorption. Single-cell RNA sequencing revealed that, under periodontitis conditions, CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells exhibited enhanced differentiation toward Th17 cells and increased glycolysis. The 2-DG hydrogel inhibited CD4\n                      <jats:sup>+<\/jats:sup>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1767931","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:33:43Z","timestamp":1771997623000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A thermosensitive hydrogel encapsulating 2-DG alleviates periodontitis by inhibiting glycolysis and effector response of Th17 cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruowen","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Prosthodontics, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji Research Institute of Stomatology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji Research Institute of Stomatology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhao","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji Research Institute of Stomatology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabao","family":"Xu","sequence":"additional","affiliation":[{"name":"W\u00fcrzburg Institute of Systems Immunology, Max Planck Research Group, Julius-Maximilians University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Stomatological Hospital, School of Stomatology, Institutes of Biomedical Sciences, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji Research Institute of Stomatology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji Research Institute of Stomatology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayao","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji Research Institute of Stomatology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji Research Institute of Stomatology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.4049\/jimmunol.1202194","article-title":"IL-17 receptor A signaling is protective in infection-stimulated periapical bone destruction","volume":"191","author":"AlShwaimi","year":"2013","journal-title":"J. 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