{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:24:39Z","timestamp":1793042679394,"version":"4.5.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Aging impairs immunity, sustains chronic inflammation, and enhances autoimmunity\u2013a process termed \u201cimmunosenescence\u201d that contributes to the pathogenesis of type 2 diabetes and rheumatoid arthritis (RA). Post-pubertal thymic involution depletes na\u00efve T-cell pool, promoting the emergence of senescent CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. To maintain T-cell homeostasis, these cells undergo extensive homeostatic proliferation, eventually reaching their replicative limit. Characterized by PD-1 and CD153 expression, these senescent cells exhibit diminished proliferative capacity and an enhanced senescence-associated secretory phenotype (SASP). While chronic periodontitis, which typically affects middle-aged individuals, is known to influence systemic conditions like RA (periodontal medicine), the underlying mechanisms remain elusive. This study investigates whether periodontitis accelerates CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell senescence and its subsequent impact on systemic disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      BALB\/c mice (5\u201342 weeks old) underwent silk ligation of the maxillary second molars to induce experimental periodontitis (LIP). Splenic CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were isolated and stimulated with IL-2, and anti-TCR\u03b2\/CD28 antibodies for 1\u20133 days to promote T-cell activation and expansion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Although the frequency of PD-1\n                      <jats:sup>+<\/jats:sup>\n                      CD153\n                      <jats:sup>+<\/jats:sup>\n                      cells did not differ significantly between the LIP and control groups\n                      <jats:italic>in vivo<\/jats:italic>\n                      , the LIP group showed significantly higher proportion of these double-positive cells following\n                      <jats:italic>in vitro<\/jats:italic>\n                      stimulation, peaking at 18 weeks. The LIP group further exhibited elevated SASP cytokine levels, an increased prevalence of senescence-associated \u03b2-galactosidase (SA \u03b2-gal)-positive cells and a reduced proportion of cells in the S phase, indicating accelerated senescence. RNA-seq analysis revealed numerous differentially expressed genes (DEGs) related to senescence in unstimulated helper T cells from the LIP group. Finally, adoptive transfer of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells from the LIP group into nude mice exacerbated collagen antibody-induced arthritis (CAIA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that severe periodontal inflammation induces a \u201csenescence-primed\u201d status in the helper T cells. These senescent cells may enter systemic circulation and exacerbate RA, highlighting a novel cellular mechanism linking periodontitis to systemic disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1806138","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:04:27Z","timestamp":1779775467000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Ligature-induced periodontitis in mice potentially accelerates CD4+ T-cell senescence and exacerbates rheumatoid arthritis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jinfeng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University","place":["Fukuoka, 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