Ebi3 knockout aggravates experimental periodontitis via Th17 polarization

J Clin Periodontol. 2023 Oct;50(10):1406-1418. doi: 10.1111/jcpe.13859. Epub 2023 Aug 3.

Abstract

Aim: To investigate the role of Ebi3-related cytokines (i.e., interleukin [IL]-35 and/or IL-27) in experimental periodontitis using Ebi3 knockout (KO) mice.

Materials and methods: The maxillary right second molar teeth of Ebi3 KO mice and C57BL/6 mice were tied with a silk ligature to induce periodontitis. Three days after ligation, gingival tissues were collected for gene expression analyses. Five days after ligation, the maxillae were removed for haematoxylin and eosin staining and immunohistochemistry. Seven days after ligation, the maxillae were removed for micro-computed tomography.

Results: The ligated side of Ebi3 KO mice showed intense alveolar bone resorption, which was substantially more pronounced than in wild-type (WT) mice. IL-17A expression was significantly higher in the gingiva of the ligated side of Ebi3 KO mice compared with WT mice. IL-10 expression was significantly lower in Ebi3 KO mice than in WT mice. The ligature-induced alveolar bone resorption in Ebi3 KO mice that received recombinant IL-35 injection was significantly less compared with that in Ebi3 KO mice that received control injection.

Conclusions: Together, these findings suggest that Th17 cells exacerbate experimental periodontitis in mice lacking Ebi3 and that IL-35 may play a critical role in inhibiting periodontal tissue destruction.

Keywords: cytokines; gene therapy; inflammation; pathogenesis; periodontal disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss*
  • Animals
  • Disease Models, Animal
  • Mice
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens / genetics
  • Periodontitis* / metabolism
  • Receptors, Cytokine
  • Th17 Cells
  • X-Ray Microtomography

Substances

  • Ebi3 protein, mouse
  • Minor Histocompatibility Antigens
  • Receptors, Cytokine