AIM2-Driven Inflammation in Periodontitis: Mechanisms and Systemic Implications

Zhen Fan,1,* Rui Chen,1,* Xiaomei Xie,1 Zhifeng Chen,1 Dan Yang,1 Chunbo Hao,1 Shan Wang2 1Affliated Hainan Hospital of Hainan Medical University (Hainan General Hospital), Haikou, 570100, People’s Republic of China; 2Department of Oral Pathology, School of Stomatology, Hainan Medical University, Haikou, 571199, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunbo Hao, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, 570100, People’s Republic of China, Email [email protected] Shan Wang, Department of Oral Pathology, School of Stomatology, Hainan Medical College, Haikou, 571199, People’s Republic of China, Email [email protected] and Objective: Periodontitis is a chronic inflammatory condition that can be associated with systemic diseases like diabetes and cardiovascular disease. This study investigates the role of AIM2, a key inflammasome component, in periodontitis, focusing on its involvement in inflammation, DNA repair, and systemic disease links.Methods: AIM2 expression was analyzed in saliva and gingival crevicular fluid (GCF) from periodontitis patients. A mouse periodontitis model and in vitro gingival fibroblast experiments were used to study AIM2’s role. Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) network analysis explored AIM2’s systemic disease associations.Results: AIM2 was significantly upregulated in periodontitis patients and models, correlating with increased IL-1β, ASC, and Caspase-1. Immunofluorescence revealed AIM2’s nuclear localization and co-localization with inflammatory markers. GSEA linked high AIM2 expression to cardiovascular diseases, while its suppression showed protective effects. PPI analysis identified interactions with DNA repair proteins (THOC2, SETX, ATM), suggesting a role in genomic stability and systemic disease.Conclusion: AIM2 drives local inflammation in periodontitis and may connect periodontitis to systemic diseases via DNA repair and systemic inflammation. This highlights AIM2 as a potential therapeutic target for managing periodontitis and associated systemic risks.Clinical Significance: Targeting AIM2 could offer a dual therapeutic strategy to control periodontal inflammation and mitigate systemic disease risks, such as cardiovascular disorders.Keywords: periodontitis, AIM2, inflammasome, systemic diseases, DNA repair