Regulatory B cells ameliorate experimental periodontitis through promoting macrophage-mediated pro-resolving functions 2300751

Abstract

Abstract Introduction This study aimed to determine the role of B10 in the induction of pro-resolving macrophage function and the resolution of experimental periodontitis. Methods A combination of ligation and P. gingivalis infection was used to establish experimental periodontitis in C57BL/6 mice. Enriched B10 cells were adoptively transferred to recipient mice via tail vein injection. In some experiments, macrophages were depleted by intraperitoneal injection of clodronate liposomes. Alveolar bone resorption was evaluated using Micro-CT. TRAP staining was performed to identify osteoclasts. In vivo imaging was used to track the macrophages and adoptively transferred-B10 cells in mice. The expression of specialized pro-resolving mediators was detected by Mass Spectrometry (LC-MS/MS). The CD68+CD206+ pro-resolving macrophages, CD68+LC3B+ autophagic cells and CD68+Ly6G+ neutrophils were detected by immunofluorescence. Results B10 transfer inhibited alveolar bone resorption and osteoclast activation. A significant increase in IL-10, Arg-1, and YM-1 expression in periodontal tissues following B10 transfer, accompanied by a marked decrease in IL-17A, TNF-α, and IL-1β expression. B10 transfer promoted the expression of pro-resolving macrophages compared with the control groups. The expressions of ATG5+, LC3B+, CD68+LC3B+ and CD68+Ly6G+ cells were elevated in the B10 transfer group. However, the B10-mediated suppression of inflammation and alveolar bone resorption was attenuated upon macrophage depletion. B10 transfer enhanced the production of the SPMs in periodontitis, such as RvD4 and RvD2. Notably, B10 cells promoted RvD2 synthesis in a macrophage-dependent manner. Conclusion This study demonstrated that B10 promoted macrophage-mediated release of specialized pro-resolving mediators and autophagy function, which represent as novel mechanism in B10-induced inhibition of inflammation and bone loss in experimental periodontitis. Funding Source NIH NIDCR R01DE025255 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)