Age-related changes of CD4+ T cell migration and cytokine expression in germ-free and SPF mice periodontium

Koichiro Irie, Takaaki Tomofuji, Daisuke Ekuni, Daiki Fukuhara, Yoko Uchida, Kota Kataoka, Shuichiro Kobayashi, Takeshi Kikuchi, Akio Mitani, Yoshihiro Shimazaki, Manabu Morita

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Objective Increasing age is a potential risk factor for periodontal tissue breakdown, which may be affected by commensal flora. The aim of this study evaluated age-related changes in CD4+ T cells, C-C chemokine ligand 5 (CCL5), interleukin (IL)-17A, and receptor activator of nuclear factor-kappa B ligand (RANKL) expression using germ-free (GF) and conventionally reared (SPF) mice. Design GF and SPF mice at 8 (n = 6/group) and 22 weeks old (n = 6/group) were used. Immunohistochemical analyses were performed to determine the effects of aging on protein expression in periodontal tissues. Age-related changes in alveolar bone were quantified using micro-CT analysis. Results SPF mice, but not GF mice, showed an age-related increase in alveolar bone loss (P < 0.01). SPF mice at 22 weeks of age increased expression of CD4+ T cells, CCL5, IL-17A, and RANKL compared to those at 8 weeks of age in connective tissue and alveolar bone surface (P < 0.01). Furthermore, there was increased CD4+ T cells, which were co-expressed with IL-17A and RANKL in SPF mice at 22 weeks of age. On the other hand, the GF mice did not show any significant differences in CD4+ T cells, CCL5, IL-17A and RANKL expression between the two age groups. Conclusions SPF mice induced an age-related increase in CD4+ T cells co- expressed with IL-17A and RANKL, with occurring alveolar bone loss. In contrast, GF mice did not show age-related changes in CD4+ T cell migration and cytokine expression.

Original languageEnglish
Pages (from-to)72-78
Number of pages7
JournalArchives of Oral Biology
Publication statusPublished - Mar 2018


  • Host response
  • Inflammation and innate immunity
  • Pathogenesis of periodontal disease
  • T-cell biology

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Dentistry(all)
  • Cell Biology


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