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单细胞 RNA 测序揭示了非手术牙周治疗后牙周炎患者免疫反应的再平衡。

Single-cell RNA sequencing reveals rebalancing of immunological response in patients with periodontitis after non-surgical periodontal therapy.

机构信息

Convergence Medical Sciences, Pusan National University, 50612, Yangsan, Republic of Korea.

Department of Periodontology, School of Dentistry, Pusan National University, 50612, Yangsan, Republic of Korea.

出版信息

J Transl Med. 2022 Nov 3;20(1):504. doi: 10.1186/s12967-022-03702-2.

Abstract

BACKGROUND

Periodontitis is a major inflammatory disease of the oral mucosa that is not limited to the oral cavity but also has systemic consequences. Although the importance of chronic periodontitis has been emphasized, the systemic immune response induced by periodontitis and its therapeutic effects remain elusive. Here, we report the transcriptomes of peripheral blood mononuclear cells (PBMCs) from patients with periodontitis.

METHODS

Using single-cell RNA sequencing, we profiled PBMCs from healthy controls and paired pre- and post-treatment patients with periodontitis. We extracted differentially expressed genes and biological pathways for each cell type and calculated activity scores reflecting cellular characteristics. Intercellular crosstalk was classified into therapy-responsive and -nonresponsive pathways.

RESULTS

We analyzed pan-cellular differentially expressed genes caused by periodontitis and found that most cell types showed a significant increase in CRIP1, which was further supported by the increased levels of plasma CRIP1 observed in patients with periodontitis. In addition, activated cell type-specific ligand-receptor interactions, including the BTLA, IFN-γ, and RESISTIN pathways, were prominent in patients with periodontitis. Both the BTLA and IFN-γ pathways returned to similar levels in healthy controls after periodontal therapy, whereas the RESISTIN pathway was still activated even after therapy.

CONCLUSION

These data collectively provide insights into the transcriptome changes and molecular interactions that are responsive to periodontal treatment. We identified periodontitis-specific systemic inflammatory indicators and suggest unresolved signals of non-surgical therapy as future therapeutic targets.

摘要

背景

牙周炎是一种主要的口腔黏膜炎症性疾病,不仅局限于口腔,还会产生全身后果。尽管慢性牙周炎的重要性已得到强调,但牙周炎引起的全身免疫反应及其治疗效果仍不清楚。在这里,我们报告了牙周炎患者外周血单核细胞(PBMC)的转录组。

方法

我们使用单细胞 RNA 测序,对健康对照者和配对的牙周炎患者治疗前后的 PBMC 进行了分析。我们提取了每个细胞类型的差异表达基因和生物途径,并计算了反映细胞特征的活性评分。细胞间串扰分为治疗反应和非反应途径。

结果

我们分析了由牙周炎引起的全细胞差异表达基因,发现大多数细胞类型的 CRIP1 显著增加,这一结果得到了牙周炎患者血浆 CRIP1 水平升高的进一步支持。此外,在牙周炎患者中,激活的细胞类型特异性配体-受体相互作用,包括 BTLA、IFN-γ 和 RESISTIN 途径,尤为突出。BTLA 和 IFN-γ 途径在牙周治疗后均恢复到健康对照组的相似水平,而 RESISTIN 途径即使在治疗后仍保持激活状态。

结论

这些数据共同提供了对牙周治疗有反应的转录组变化和分子相互作用的深入了解。我们确定了牙周炎特异性全身炎症指标,并提出了非手术治疗未解决的信号作为未来的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35da/9635198/101cf3b40755/12967_2022_3702_Fig1_HTML.jpg

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