{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:37:59Z","timestamp":1792546679967,"version":"4.5.0"},"reference-count":31,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Diabetic periodontitis (DPD) is recognized as a common complication of diabetes mellitus. It progresses rapidly and causes severe destruction of periodontal tissues. The condition often leads to a poor prognosis for affected patients. CD4\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes\u2014pivotal effector cells in adaptive immunity\u2014play a central role in driving DPD pathogenesis through immunometabolic dysregulation. The functional dynamics and contributions of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells to DPD pathogenesis remain insufficiently investigated. To investigate this, single-cell RNA sequencing data from the gingival tissues of DPD mice in the Gene Expression Omnibus database were analyzed, identifying significant CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell senescence in DPD. This finding was experimentally confirmed using a DPD mouse model. Furthermore, through adoptive transfer experiments, we demonstrated that in DPD, senescent CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells exacerbate the release of senescence-associated secretory phenotype (SASP). SASP chemokines recruit immune cells, which in turn release additional inflammatory factors, creating a self-amplifying cycle that disrupts the Th17\/Treg balance and worsens bone loss. This reveals the pathogenic role of senescent CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, whereas adoptive transfer of normal CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells rescues this pathological process. Bioinformatics analysis linked CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell senescence to the JAK-STAT and p38 MAPK signaling pathways. Subsequent experimental validation detected upregulated JAK-STAT and p38 MAPK activity in DPD gingival tissues. Pharmacological inhibition of these pathways in vitro markedly reduced CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell senescence. Mechanistically, JAK-STAT activation elevated mitochondrial reactive oxygen species (mtROS), subsequently triggering the tumor necrosis factor \u03b1 (TNF-\u03b1)\u2013p38 MAPK axis. This cascade led to p53 upregulation and enhanced cellular senescence. This study clarifies the immunopathological mechanisms underlying CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell senescence in DPD, emphasizing the crosstalk between metabolic dysregulation via JAK-STAT-mtROS and inflammatory signaling through TNF-\u03b1\u2013p38 MAPK (proinflammatory signaling cascade). These findings provide novel perspectives for developing therapeutic strategies targeting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell senescence in DPD, thereby mitigating inflammatory factor release and inhibiting alveolar bone resorption.\n                  <\/jats:p>","DOI":"10.1177\/00220345251400253","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T04:52:01Z","timestamp":1766033521000},"page":"1174-1185","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Senescent CD4\n                    <sup>+<\/sup>\n                    T Cells Drive Diabetic Periodontitis via JAK-STAT-ROS-p38 MAPK"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4821-3272","authenticated-orcid":false,"given":"M.","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"},{"name":"Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3604-0356","authenticated-orcid":false,"given":"L.","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"},{"name":"Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6234-2852","authenticated-orcid":false,"given":"X.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"},{"name":"Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6149-6319","authenticated-orcid":false,"given":"Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"},{"name":"Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4872-402X","authenticated-orcid":false,"given":"R.","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"},{"name":"Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0104-8802","authenticated-orcid":false,"given":"S.","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3185-0887","authenticated-orcid":false,"given":"H.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"},{"name":"Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, Shandong, China"},{"name":"Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9980-1382","authenticated-orcid":false,"given":"M.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"},{"name":"Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, Shandong, China"},{"name":"School of Clinical Medicine, Jining Medical University, Jining, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Ahmad P Estrin N Farshidfar N Zhang Y Miron RJ. 2025. 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