TRIM31: A Novel Guardian Against Periodontal Inflammation via Modulation of NLRP3 Inflammasome and Macrophage Polarization
- Immunol Invest. 2026 Jun 22:1-21. doi: 10.1080/08820139.2026.2680504.
- 1. Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China.
- 2. Department of Implant Dentistry，Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China.
- 3. Department of Periodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China.
Background: Periodontitis involves dysregulated immunity where the NLRP3 inflammasome plays a key role, while the role of TRIM31, an E3 ubiquitin Ligase, remains unknown in periodontitis.
Methods: Human gingival fibroblasts (HGFs) and macrophages were stimulated with LPS and ATP; TRIM31 was overexpressed via AAV, and NLRP3 was knocked out via CRISPR; periodontitis was induced in WT and NLRP3-KO mice treated with AAV-TRIM31; bone loss, osteoclasts, and Apoptosis were assessed.
Results: TRIM31 was downregulated in inflammation and correlated with M2 polarization. TRIM31 overexpression protected HGFs, promoted M2 polarization, and bound to NLRP3, thereby promoting K48-linked ubiquitination and degradation. In vivo, TRIM31 reduced bone loss, osteoclasts, and apoptosis; these effects were abolished in NLRP3-KO cells and mice.
Conclusion: TRIM31 negatively regulates periodontal inflammation via ubiquitin-dependent NLRP3 degradation.