Dataset Information

Immunological link between periodontitis and type 2 diabetes deciphered by single-cell RNA analysis.

ABSTRACT:

Background

Type 2 diabetes mellitus (DM) is a complex metabolic disorder that causes various complications, including periodontitis (PD). Although a bidirectional relationship has been reported between DM and PD, their immunological relationship remains poorly understood. Therefore, this study aimed to compare the immune response in patients with PD alone and in those with both PD and DM (PDDM) to expand our knowledge of the complicated connection between PD and DM.

Methods

Peripheral blood mononuclear cells were collected from 11 healthy controls, 10 patients with PD without DM, and six patients with PDDM, followed by analysis using single-cell RNA sequencing. The differences among groups were then compared based on intracellular and intercellular perspectives.

Results

Compared to the healthy state, classical monocytes exhibited the highest degree of transcriptional change, with elevated levels of pro-inflammatory cytokines in both PD and PDDM. DM diminished the effector function of CD8+ T and natural killer (NK) cells as well as completely modified the differentiation direction of these cells. Interestingly, a prominent pathway, RESISTIN, which is known to increase insulin resistance and susceptibility to diabetes, was found to be activated under both PD and PDDM conditions. In particular, CAP1+ classical monocytes from patients with PD and PDDM showed elevated nuclear factor kappa B-inducing kinase activity.

Conclusions

Overall, this study elucidates how the presence of DM contributes to the deterioration of T/NK cell immunity and the immunological basis connecting PD to DM.

SUBMITTER: Lee H

PROVIDER: S-EPMC10713875 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Immunological link between periodontitis and type 2 diabetes deciphered by single-cell RNA analysis.

Lee Hansong H Joo Ji-Young JY Song Jae-Min JM Kim Hyun-Joo HJ Kim Yun Hak YH Park Hae Ryoun HR

Clinical and translational medicine 20231201 12

<h4>Background</h4>Type 2 diabetes mellitus (DM) is a complex metabolic disorder that causes various complications, including periodontitis (PD). Although a bidirectional relationship has been reported between DM and PD, their immunological relationship remains poorly understood. Therefore, this study aimed to compare the immune response in patients with PD alone and in those with both PD and DM (PDDM) to expand our knowledge of the complicated connection between PD and DM.<h4>Methods</h4>Periph ...[more]

PMID: 38082425

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Project description:Single-cell RNA sequencing (scRNA-seq) enables specific profiling of cell populations at single-cell resolution. The osteoimmunology microenvironment in the occurrence and development of periodontitis remains poorly understood at the single-cell level. In this study, we used single-cell transcriptomics to comprehensively reveal the complexities of the molecular components and differences with counterparts residing in periodontal tissues. Methods: We performed scRNA-seq to identify 51248 single cells from healthy controls (n=4), patients with severe chronic periodontitis (n=5), and patients with severe chronic periodontitis after initial periodontal therapy within 1 month (n=3). Uniform manifold approximation and projection (UMAP) were further conducted to explore the cellular composition of periodontal tissues. Pseudotime cell trajectory and RNA velocity analysis, combined with gene enrichment analysis were used to reveal the molecular pathways underlying cell fate decisions. CellPhoneDB were performed to identify ligand-receptor pairs among the major cell types in the osteoimmunology microenvironment of periodontal tissues. Results: A cell atlas of the osteoimmunology microenvironment in periodontal tissues was characterized and included ten major cell types, such as fibroblasts, monocytic cells, endothelial cells, and T and B cells. The enrichment of TNFRSF21+ fibroblasts with high expression of CXCL1, CXCL2, CXCL5, CXCL6, CXCL13, and IL24 was detected in patients with periodontitis compared to healthy individuals. The fractions of CD55+ mesenchymal stem cells (MSCs), APOE+ pre-osteoblasts (pre-OBs), and IBSP+ osteoblasts decreased significantly in response to initial periodontal therapy. In addition, CXCL12 + MSC-like pericytes could convert their identity into a pre-OB state during inflammatory responses even after initial periodontal therapy confirmed by single-cell trajectory. Moreover, we portrayed the distinct subtypes of monocytic cells and abundant endothelial cells significantly involved in the immune response. The heterogeneity of T and B cells in periodontal tissues was characterized. Finally, we mapped osteoblast/osteoclast differentiation mediators to their source cell populations by identifying ligand-receptor pairs and highlighted the effects of Ephrin-Eph signaling on bone regeneration after initial periodontal therapy. Conclusions: Our analyses uncovered striking spatiotemporal dynamics in gene expression, population composition, and cell-cell interactions during periodontitis progression. These findings provide insights into the cellular and molecular underpinning of periodontal bone regeneration.

Project description:Background: Relationship between periodontitis (PD) and type 1 diabetes (T1D) has been reported, but the detailed pathogenesis requires further elucidation. This study aimed to reveal the genetic linkage between PD and T1D through bioinformatics analysis, thereby providing novel insights into scientific research and clinical treatment of the two diseases. Methods: PD-related datasets (GSE10334, GSE16134, GSE23586) and T1D-related datasets(GSE162689)were downloaded from NCBI Gene Expression Omnibus (GEO). Following batch correction and merging of PD-related datasets as one cohort, differential expression analysis was performed (adjusted p-value <0.05 and ∣log2 fold change| > 0.5), and common differentially expressed genes (DEGs) between PD and T1D were extracted. Functional enrichment analysis was conducted via Metascape website. The protein-protein interaction (PPI) network of common DEGs was generated in The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Hub genes were selected by Cytoscape software and validated by receiver operating characteristic (ROC) curve analysis. Results: 59 common DEGs of PD and T1D were identified. Among these DEGs, 23 genes were commonly upregulated, and 36 genes were commonly downregulated in both PD- and T1D-related cohorts. Functional enrichment analysis indicated that common DEGs were mainly enriched in tube morphogenesis, supramolecular fiber organization, 9 + 0 non-motile cilium, plasma membrane bounded cell projection assembly, glomerulus development, enzyme-linked receptor protein signaling pathway, endochondral bone morphogenesis, positive regulation of kinase activity, cell projection membrane and regulation of lipid metabolic process. After PPI construction and modules selection, 6 hub genes (CD34, EGR1, BBS7, FMOD, IGF2, TXN) were screened out and expected to be critical in linking PD and T1D. ROC analysis showed that the AUC values of hub genes were all greater than 70% in PD-related cohort and greater than 60% in T1D-related datasets. Conclusion: Shared molecular mechanisms between PD and T1D were revealed in this study, and 6 hub genes were identified as potential targets in treating PD and T1D.

Dataset Information

Immunological link between periodontitis and type 2 diabetes deciphered by single-cell RNA analysis.

Background

Methods

Results

Conclusions

Publications

Immunological link between periodontitis and type 2 diabetes deciphered by single-cell RNA analysis.

Similar Datasets

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