Source: openalex · Origin: JP · J LI, Terukazu Sanui, Miyu Shida, Karen Yotsumoto, Mwannes Ahmad · Frontiers in Immunology · 2026-05-26
URL: https://doi.org/10.3389/fimmu.2026.1806138
AI rationale (4/5, tier: preliminary): Mouse periodontitis model bridging senescence (SASP, CD4+ T cells) to RA via chronic inflammation; fits INCLUDE criteria but animal study limits tier.
Introduction Aging impairs immunity, sustains chronic inflammation, and enhances autoimmunity–a process termed “immunosenescence” that contributes to the pathogenesis of type 2 diabetes and rheumatoid arthritis (RA). Post-pubertal thymic involution depletes naïve T-cell pool, promoting the emergence of senescent CD4 + 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 + T-cell senescence and its subsequent impact on systemic disease. Methods BALB/c mice (5–42 weeks old) underwent silk ligation of the maxillary second molars to induce experimental periodontitis (LIP). Splenic CD4 + T cells were isolated and stimulated with IL-2, and anti-TCRβ/CD28 antibodies for 1–3 days to promote T-cell activation and expansion. Results Although the frequency of PD-1 + CD153 + cells did not differ significantly between the LIP and control groups in vivo , the LIP group showed significantly higher proportion of these double-positive cells following in vitro stimulation, peaking at 18 weeks. The LIP group further exhibited elevated SASP cytokine levels, an increased prevalence of senescence-associated β-galactosidase (SA β-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 + T cells from the LIP group into nude mice exacerbated collagen antibody-induced arthritis (CAIA). Conclusions These findings suggest that severe periodontal inflammation induces a “senescence-primed” 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.