Featured Immune Characteristics of Periodontitis and Primary Sjögren's Syndrome Revealed by Single‐Cell Transcriptome Analyses

ABSTRACT Periodontitis (PD) and primary Sjögren's syndrome (pSS) are persistent inflammatory diseases that affect oral health, and numerous studies have uncovered phenotypic and intrinsic correlations between the two. However, a comprehensive and high‐resolution analysis at the single‐cell level has not been reported comparing the immune cell landscapes in PD and pSS. This study integrated single‐cell transcriptome data from peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), PD and pSS patients sourced from the NCBI and NGDC databases. The scRNA datasets were integrated, and cells were clustered using Seurat, with further subdivision of T/NK, myeloid cells and B cell subclusters. Next, NicheNetr was used to analyse the communication between myeloid cells and CD8 + naive T (Tn) cells. Finally, we identified nine T/NK cell subclusters, seven myeloid cell subclusters and five B cell subclusters. Compared to the HC group, the proportion of CD8 + Tn cells was significantly downregulated in both PD and pSS. HLA‐DRA + mono cells showed a significant decrease in PD. Additionally, immature B cells were upregulated in PD but showed an opposite trend in pSS. The intracellular communication analysis between myeloid cells and CD8 + Tn cells suggested that myeloid cells may promote the exhaustion of CD8 + Tn cells through the IL‐7/TNFSF11‐CDKN1A signalling pathways. The BACE2‐CDKN1A signalling pathway may also contribute to the depletion of CD8 + Tn cells in both PD and pSS. Collectively, this study uncovers the single‐cell level associations between PD and pSS, providing new insights into the common molecular mechanisms underlying these two diseases.