Single-Cell Transcriptome Atlas of the Canine Peri-implantitis Reveals stromal–immune cells interaction

Abstract Background Most current research has focused on the entire periodontal tissue, which restricts a comprehensive understanding of the heterogeneity between gingiva and bone tissues, and hinders the development of targeted host therapies for peri-implantitis. To uncover the pathogenic mechanisms of peri-implantitis, our study employed a tissue-specific approach to investigate the interactions between stromal and immune cells in gingiva and bone tissues separately, using single-cell sequencing techniques. This strategy aims to develop the insights of the pathogenesis of peri-implantitis, providing a scientific basis for the treatment of peri-implantitis. Methods Single-cell RNA sequencing transcriptomics profiling was conducted on samples from peri-implantitis-affected and healthy beagle dogs. Flow cytometry was utilized to further verify the identified subclusters and their involvement in peri-implantitis. Results In peri-implantitis, inflammation-associated cells increased, exhibiting distinct subclusters in gingival and bone tissues. In gingival tissues, IL6+ endothelial cells, IL18BP+ endothelial cells, and CXCL8+ fibroblasts played significant roles. APOD+ fibroblasts were predominantly found in bone tissues, while SFN+ fibroblasts were present in both tissues. Additionally, a unique ligand-receptor pair, C3 (APOD+ fibroblast) – C3AR1 (Monocyte/ Macrophage), was identified in bone tissue. Conclusions Stromal cells exert distinct regulatory influences on immune cells in gingival and bone tissues during peri-implantitis, offering new perspectives for studying the pathogenic mechanisms of the disease.