The NF-κB Signalling Regulates the Abnormal Functions of Neutrophils in Severe Periodontal Disease

  • Int Dent J. 2025 Oct 25;75(6):103973. doi: 10.1016/j.identj.2025.103973.
Wei Lu  1 ,  Yue Tong  1 ,  Jiaming Cheng  2 ,  Xianxin Zhu  3 ,  Jin Li  3 ,  Chen Yang  4 ,  Haixia Gu  4 ,  Yunong Wu  5 ,  Changsong Lin  6
Affiliations
  • 1. Department of Periodontology, the Affiliated Stomatological Hospital of Nanjing Medical University, 210029, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, 210029, Nanjing, China.
  • 2. Department of Bioinformatics, Nanjing Medical University, 211166, Nanjing, Jiangsu, China.
  • 3. State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, 210029, Nanjing, China.
  • 4. Department of Periodontology, the Affiliated Stomatological Hospital of Nanjing Medical University, 210029, Nanjing, China.
  • 5. State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, 210029, Nanjing, China; Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Nanjing Medical University, 210029, Nanjing, China. Electronic address: [email protected].
  • 6. Department of Bioinformatics, Nanjing Medical University, 211166, Nanjing, Jiangsu, China. Electronic address: [email protected].
PMID: 41145025 DOI: 10.1016/j.identj.2025.103973
Abstract

Objectives: To explore the regulatory mechanism of neutrophils in severe periodontitis (PDs), given their link to periodontal inflammation progression (PDs).

Methods: Single-cell RNA-seq and bulk RNA transcriptome data from GEO were analysed using ClusterProfiler for DEG enrichment, hdWGCNA to identify neutrophil-linked module genes, pySCENIC for specific regulons, co-immunostaining for protein expression, and LPS-stimulated human gingival neutrophils with Real-Time PCR for inflammatory factors.

Results: Neutrophils in PDs showed activated inflammatory response and NF-κB signalling, acting as key mediators in cell-cell communication. hdWGCNA identified 7 modules, with transcription factor Nrf2 highly specific to PD neutrophils. NFKB1 was upregulated, and NF-κB inhibition reduced LPS-induced IL2, IL8, and TGFβ production.

Conclusions: Neutrophils are central to PDs, with activated NF-κB pathways. Clinically, targeting NF-κB reduces gingivitis-induced inflammatory cytokines.

Clinical significance: Specific inhibition of the NF-κB signalling pathway can reduce the expression of Porphyromonas gingivalis LPS-induced inflammatory cytokines.

Keywords
Neutrophils; Periodontitis; Regulatory network; scRNA-seq.
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