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

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 CD1d hi 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.