Regulatory B cells induced by interleukin-35 inhibit inflammation and alveolar bone resorption in ligature-induced periodontitis

J Periodontol. 2023 Nov;94(11):1376-1388. doi: 10.1002/JPER.23-0038. Epub 2023 May 9.

Abstract

Background: Regulatory B cells (Bregs) have been reported to suppress immune responses and alveolar bone loss in murine periodontitis models. These cells could be induced by interleukin (IL)-35 which is increased upon periodontal inflammation. Thus, this study aimed to explore the role of Bregs induced by IL-35 in periodontitis.

Methods: Experimental periodontitis was induced in mice by ligature. Two weeks after ligation, the test group was systemically treated with IL-35 for 1 week. Four weeks after ligation, all mice were euthanized, and alveolar bone loss was evaluated by microcomputed tomography. Cytokines associated with periodontitis were analyzed using reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Bregs in spleens, cervical lymph nodes, and periodontal tissues were detected by flow cytometry and immunofluorescence staining.

Results: In the mouse model of periodontitis, IL-35 induced the expansion of CD1dhi CD5+ B10 cells with increased interleukin-10 (IL-10) and IL-35 production. IL-35 administration also attenuated alveolar bone loss and reduced the levels of proinflammatory cytokines in situ.

Conclusions: Following ligature-induced periodontitis in mice, IL-35 inhibited periodontal inflammation and alveolar bone resorption at least partially through the induction of B10 cells and IL-35+ Bregs.

Keywords: B-lymphocytes; immunity; inflammation; interleukin-35; periodontitis.

MeSH terms

  • Alveolar Bone Loss* / drug therapy
  • Animals
  • B-Lymphocytes, Regulatory* / pathology
  • Cytokines
  • Inflammation
  • Mice
  • Periodontitis* / complications
  • X-Ray Microtomography

Substances

  • Cytokines