Proteomic and single-cell analysis shed new light on the anti-inflammatory role of interferonβ in chronic periodontitis

Jieying Liu; Tianle Li; Shunhao Zhang; Eryi Lu; Wei Qiao; Huimin Chen; Peng Liu; Xiaoyue Tang; Tianfan Cheng; Hui Chen

doi:10.3389/fphar.2023.1232539

Proteomic and single-cell analysis shed new light on the anti-inflammatory role of interferonβ in chronic periodontitis

Front Pharmacol. 2023 Oct 9:14:1232539. doi: 10.3389/fphar.2023.1232539. eCollection 2023.

Authors

Jieying Liu^#¹, Tianle Li^#², Shunhao Zhang³, Eryi Lu⁴, Wei Qiao², Huimin Chen², Peng Liu¹, Xiaoyue Tang¹, Tianfan Cheng², Hui Chen²

Affiliations

¹ Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
² Faculty of Dentistry, Prince Philip Dental Hospital, University of Hong Kong, Pokfulam, China.
³ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
⁴ Department of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

^# Contributed equally.

Abstract

Periodontitis, a condition that results in periodontal attachment loss and alveolar bone resorption, contributes to the global burden of oral disease. The underlying mechanism of periodontitis involves the dysbiosis and dyshomeostasis between host and oral microbes, among which the macrophage is one of the major innate immune cell players, producing interferon β (IFNβ) in response to bacterial infection. The objective of this research was to examine the interaction of macrophages with periodontitis and the role and mechanism of IFNβ on macrophages. IFNβ has been shown to have the potential to induce the differentiation of M1 to M2 macrophages, which are stimulated by low levels of lipopolysaccharide (LPS). Additionally, IFNβ has been demonstrated to promote the production of ISG15 by macrophages, which leads to the inhibition of the innate immune response. Moreover, our investigation revealed that IFNβ has the potential to augment the secretion of ISG15 and its downstream cytokine, IL10, in LPS-stimulated macrophages. Single-cell analysis was conducted on the gingival tissues of patients with periodontitis, which revealed a higher proportion of macrophages in the periodontitis-diseased tissue and increased expression of IFNβ, ISG15, and IL10. Gene Set Enrichment Analysis indicated that bacterial infection was associated with upregulation of IFNβ, ISG15, and IL10. Notably, only IL10 has been linked to immunosuppression, indicating that the IFNβ-ISG15-IL10 axis might promote an anti-inflammatory response in periodontitis through IL10 expression. It is also found that macrophage phenotype transitions in periodontitis involve the release of higher levels of IFNβ, ISG15, and IL10 by the anti-inflammatory M2 macrophage phenotype compared to the pro-inflammatory M1 phenotype and myeloid-derived suppressor cells (MDSCs). This implies that the IFNβ-induced production of IL10 might be linked to the M2 macrophage phenotype. Furthermore, cell communication analysis demonstrated that IL10 can promote fibroblast proliferation in periodontal tissues via STAT3 signaling.

Keywords: IFNβ; IL10; ISG15; chronic periodontitis; macrophage; proteomics; single-cell analysis.

Grants and funding

This study was funded by the grants from National High Level Hospital Clinical Research Funding No. 2022-PUMCH-C-023, and 2022-PUMCH-B-015, Fundamental Research Funds for the Central Universities (3332021094), and National Natural Science Foundation of China (No. 81900723).