Monocytic myeloid-derived suppressor cells contribute to the exacerbation of bone destruction in periodontitis.
Zhaocai Zhou, Chi Zhan, Wenchuan Li, Wenji Luo, Yufeng Liu, Feng He, Yaguang Tian, Zhengmei Lin, Zhi Song
Author Information
Zhaocai Zhou: Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China.
Chi Zhan: Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China.
Wenchuan Li: Guangzhou First People's Hospital, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Wenji Luo: Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China.
Yufeng Liu: Guangzhou First People's Hospital, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Feng He: Guangzhou First People's Hospital, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Yaguang Tian: Department of Stomatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China. yaguangtian@163.com.
Zhengmei Lin: Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China. linzhm@mail.sysu.edu.cn.
Zhi Song: Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China. songzh@mail.sysu.edu.cn. ORCID
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. 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-��B-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-��B signaling in PD. Furthermore, the pathway of NF-��B-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-1��, IL-6 and TNF-��. 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.
