Single-Cell Analyses of the Oral Mucosa Reveal Immune Cell Signatures

Abstract

Inflammatory bowel disease (IBD) is a common immune-related disease of the gastrointestinal tract that affects many people around the world. Extraintestinal manifestations of IBD have been frequently observed in recent years; one of these, periodontitis, has gained increasing attention. Periodontitis is a chronic inflammatory disease characterized by inflammation and destruction of periodontal tissues due to the disruption of host immune homeostasis. Clinical studies have revealed that periodontal inflammation is associated with IBD. However, the detailed heterogeneity of immune cells and their developmental relationships remain poorly understood at the single-cell level. In this study, we performed single-cell RNA (scRNA) sequencing to assess the transcriptome heterogeneity in periodontal tissues. We found the cellular composition and subclusters with specific gene expression profiles by uniform manifold approximation and projection. Pseudo-time analysis combined with gene enrichment analysis was performed to reveal cell states and key pathways. Ligand–receptor pairs revealed cell–cell communication among the immune cell types in periodontal tissues. Based on our analysis, we identified an essential role for Tcr⁺ macrophage, Prdx1⁺ neutrophil, and Mif⁺ T subpopulations with proinflammatory phenotype infiltration. Moreover, we examined the heterogeneity of monocytic cells and B cells. Collectively, the mapping of scRNA revealed the complex cellular landscape of oral mucosa immune cells and highlighted these immune cells as a previously unrecognized factor that may aggravate inflammation. Our analysis proves that periodontitis could exacerbate colitis and provides novel ideas for controlling and preventing IBD exacerbations.