Regulatory role of PDK1 via integrated gene analysis of mitochondria-immune response in periodontitis

•Mitochondria play a crucial role in regulating the immune response in periodontitis, especially of B cells.•Ten Mitochondria-immune-related differentially expressed genes were identified, the expression of which could effectively distinguish periodontitis samples from the healthy controls.•Pyruvate Dehydrogenase Kinase Isozyme 1 represents the key mitochondria-immune response-related gene regulating B-cell-mediated immune response in periodontitis, and is a potential therapeutic target for periodontitis. To investigate the association between mitochondrial events and immune response in periodontitis and related regulatory genes. Gene expression profiles in gingival tissues were retrieved from the Gene Expression Omnibus. Mitochondria-immune response-related differentially expressed genes (MIR-DEGs) between the healthy and periodontitis samples were determined. WGCNA, GO, and KEGG were used to investigate the function and the enriched pathways of MIR-DEGs. The correlation between MIR-DEGs expression and clinical probing pocket depth was analyzed. The MIR-DEGs were further identified and verified in animal samples. A periodontitis model was established in C57BL/6 mice with silk ligation. Micro-computed tomography was used to assess alveolar bone loss. Western blot, quantitative real-time polymerase chain reaction, and immunohistochemical analyses further validated the differential expression of the MIR-DEGs. A total of ten MIR-DEGs (CYP24A1, PRDX4, GLDC, PDK1, BCL2A1, CBR3, ARMCX3, BNIP3, IFI27, and UNG) were identified, the expression of which could effectively distinguish patients with periodontitis from the healthy controls. Enhanced immune response was detected in the periodontitis group with that in the healthy controls, especially in B cells. PDK1 was a critical MIR-DEG correlated with B cell immune response and clinical periodontal probing pocket depth. Both animal and clinical periodontal samples presented higher gene and protein expression of PDK1 than the control samples. Additionally, PDK1 colocalized with B cells in both animal and clinical periodontal tissues. Mitochondria participate in the regulation of the immune response in periodontitis. PDK1 may be the key mitochondria-related gene regulating B-cell immune response in periodontitis.