IL-33 Exacerbates Periodontal Disease Through Induction of RANKL

John Butcher, Jennifer Malcolm, R. A. Awang, Jessica Oliver-Bell, Lauren Campbell, Ana Adrados-Planell, Christopher Nile, Foo Liew, Shauna Culshaw

Research output: Contribution to conferenceAbstractpeer-review

49 Citations (Scopus)


Objectives: Destruction of periodontal tissues and alveolar bone loss (ABL) results from a dysregulated host immune responses to periodontal bacteria. These responses culminate in lymphocyte activation and production of RANKL, leading ultimately to enhanced osteoclastogenesis. We sought to investigate the role played by IL33, a cytokine belonging to the IL-1 family, in pathogenic alveolar bone resorptionMethods: We investigated the expression of IL33 in gingival tissue from healthy controls (n=12) and patients with chronic periodontitis (n=15). IL-33 was administered to mice in a model of periodontitis induced by oral infection with Porphyromonas gingivalis. Periodontitis was also initiated in mice lacking the IL33 receptor, ST2. Alveolar bone destruction, serum antibody and lymphocyte responses were then investigated.Results: Expression of IL33 and its receptor, ST2, were higher in gingival tissues from patients with chronic periodontitis compared with healthy tissues (p < 0.05). Similarly, IL33 expression was higher in periodontal tissues of P. gingivalis-infected mice, compared with sham-infected controls (p < 0.05). IL33 treatment of P. gingivalis-infected mice significantly exacerbated ABL compared with infection or IL33 treatment alone (p < 0.001). Conversely, P. gingivalis-induced ABL was attenuated in mice lacking ST2. The percentage of T and B lymphocytes expressing RANKL were highest in the gingival tissues of P. gingivalis-infected mice treated with IL-33 compared with P. gingivalis-infected mice treated with PBS alone (17.3 vs 8.2% of CD3+ [p < 0.01] and 22.9 vs 8.4% of CD19+, [p < 0.05]) and on T lymphocytes isolated from cervical draining lymph nodes (10.7 vs 8.2% CD3+, [p < 0.01]). In vivo inhibition of RANKL, via OPG administration, abrogated periodontal bone destruction in P. gingivalis-infected, IL33-treated mice.Conclusions: These findings demonstrate that IL33 exacerbated ABL in a RANKL-dependent manner and indicate a previously undefined pathogenic role for IL33 in periodontal disease.
Original languageEnglish
Publication statusPublished - 11 Mar 2015
EventIADR/AADR/CADR General Session & Exhibition (March 11-14, 2015) (Boston, Massachusetts) - Boston, United States
Duration: 11 Mar 201515 Mar 2015


ConferenceIADR/AADR/CADR General Session & Exhibition (March 11-14, 2015) (Boston, Massachusetts)
Country/TerritoryUnited States


  • periodontitis
  • immunology


Dive into the research topics of 'IL-33 Exacerbates Periodontal Disease Through Induction of RANKL'. Together they form a unique fingerprint.

Cite this