Background
Periodontitis (PD) is a chronic infectious and inflammatory disease characterized by alveolar bone loss. The distinctive activity of immune cells critically exacerbates bone resorption in PD. Myeloid-derived suppressor cells (MDSCs) are known to contribute to various chronic inflammatory conditions, but their role in the pathogenesis and progression of PD remains poorly understood.
Conclusions
In conclusion, this study highlights the pivotal proinflammatory role of M-MDSCs in PD and suggests that targeting these cells may represent a novel immunotherapeutic approach. Future research could focus on strategies to specifically target MDSCs for the treatment of periodontitis.
Methods
We used single-cell transcriptomic analysis with human gingival samples and animal models of experimental periodontitis to examine the role of M-MDSCs in PD. We also explored the therapeutic effect of depleting MDSCs on PD in vivo. Additionally, the mechanisms of long non-coding RNA Neat1 and the pathway of NF-κB-dependent "canonical NLRP3 inflammasome activation" in MDSCs were investigated in PD.
Results
In this study, we revealed that monocytic (M)-MDSCs were significantly increased in inflamed gingiva of PD patients compared to healthy individuals. Expansion of M-MDSCs was also observed in the mouse model of ligature-induced periodontitis, and depletion of MDSCs in PD mice could ameliorate alveolar bone loss and reduce periodontal inflammation. Mechanistically, we found that long non-coding RNA Neat1 was significantly upregulated in M-MDSCs, which achieved this proinflammatory effect by activating NF-κB signaling in PD. Furthermore, the pathway of NF-κB-dependent "canonical NLRP3 inflammasome activation" was confirmed in the PD mouse model, accompanied by increased secretion of proinflammatory cytokines that drive alveolar bone loss, including IL-1β, IL-6 and TNF-α. Conclusions: In