Type I interferon-induced CD169+ macrophages play a protective role in periodontitis.

BACKGROUND

This study aims to investigate the transcriptional characteristics and differentiation microenvironment of the CD169+ macrophages in periodontal tissues, and to explore their impact on periodontitis.

METHODS

Single-cell RNA sequencing landscape of periodontal tissues from healthy controls (n = 8) and periodontitis patients (n = 10) were constructed. Immunohistochemical staining was used to detect the percentage of CD169+ macrophages in periodontitis tissues of different severity to explore the potential links between them and periodontitis. Anti-IFNAR1 antibodies were used to block the IFNAR1 receptor in mice to validate the role of type I interferon signaling in CD169+ macrophage differentiation and its impact on the progression of periodontitis. SCENIC analysis, immunohistochemical staining, immunofluorescence staining, flow cytometry, and in vitro experiments were used to identify the surface markers, differentiation microenvironment, and regulatory mechanisms of CD169+ macrophages.

RESULTS

The phenotypes of CD169+ macrophages are characterized by CD169+, MERTK+, CX3CR1-, and CCR2-. The CD169+ macrophages could maintain immune homeostasis by producing CCL18 and IL10. The percentage of CD169+ cells in periodontal tissues was found to be negatively correlated with the severity of periodontitis. Type I interferons produced by gingival fibroblasts and keratinocytes are essential for the differentiation of CD169+ macrophages, which in turn orchestrate immunomodulation and tissue homeostasis restoration during the recovery phase of periodontitis.

CONCLUSIONS

Our findings indicate that type I interferons produced by fibroblasts in periodontal tissues induce monocytes to differentiate into macrophages with a CD169+MERTK+ phenotype. These cells play a role in negative immune regulation and may provide a positive contribution to the recovery of periodontitis.

PLAIN LANGUAGE SUMMARY: Periodontitis is one of the major diseases that threaten human health. CD169+ macrophages may play a key role in immune homeostasis by producing IL10 and CCL18. The type I interferon-IRF7 axis may induce the differentiation of macrophages into CD169+ macrophages, which in turn orchestrates immunomodulation and tissue homeostasis restoration during the recovery phase of periodontitis. Studying the functions and differentiation mechanisms of CD169+ macrophages in periodontal tissue may offer new therapeutic targets for periodontitis and provide broader benefits for overall human health.