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单细胞 RNA 测序揭示非传统 T 细胞在口腔扁平苔藓中的功能。

Function of unconventional T cells in oral lichen planus revealed by single-cell RNA sequencing.

机构信息

Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Oral Medicine, School of Stomatology, Stomatological Hospital and Dental School, Tongji University, Shanghai, 200072, China.

School of Life Sciences and Technology, Tongji University, Shanghai, China.

出版信息

Inflamm Res. 2024 Sep;73(9):1477-1492. doi: 10.1007/s00011-024-01912-6. Epub 2024 Jul 29.

DOI:10.1007/s00011-024-01912-6
PMID:39073597
Abstract

OBJECTIVE

We intended to map the single-cell profile of OLP, explore the molecular characteristics of unconventional T cells in OLP tissues.

METHODS

Buccal mucosa samples from OLP patients and healthy individuals were used to prepare single-cell suspension. Single-cell RNA sequencing was used to analyze the proportion of all the cells, and the molecular characteristics of unconventional T cells. Immunohistochemical staining was used to detect the expression of unconventional T cells marker genes.

RESULTS

The cell clusters from buccal mucosa were categorized into immune cells, fibroblasts, endothelial cells, and epithelial cells. Unconventional T cells with phenotype of CD247TRDCNCAM1 were identified. Immunohistochemical staining revealed higher expression of unconventional T cell marker genes in OLP tissue, predominantly in the lamina propria. In OLP, unconventional T cells are in a unique stress response state, exhibited enhanced NF-κB signaling and apoptosis inhibition, enhanced heat shock protein genes expression, weakened cytotoxic function. A large number of ligand-receptor pairs were found between unconventional T cells and other cells, particularly with fibroblasts and endothelial cells.

CONCLUSIONS

This study mapped the single-cell profile of OLP, delineated the molecular characteristics of unconventional T cells in OLP, and uncovered that these unconventional T cells are in a stress response state.

摘要

目的

绘制 OLP 的单细胞图谱,探索 OLP 组织中非常规 T 细胞的分子特征。

方法

使用口腔颊黏膜样本制备单细胞悬浮液,对 OLP 患者和健康个体进行单细胞 RNA 测序,分析所有细胞的比例和非常规 T 细胞的分子特征。免疫组织化学染色检测非常规 T 细胞标记基因的表达。

结果

口腔颊黏膜细胞簇可分为免疫细胞、成纤维细胞、内皮细胞和上皮细胞。鉴定出具有 CD247+TRDC+CAM1 表型的非常规 T 细胞。免疫组织化学染色显示,OLP 组织中非常规 T 细胞标记基因表达升高,主要在固有层。在 OLP 中,非常规 T 细胞处于独特的应激反应状态,表现出 NF-κB 信号增强和凋亡抑制、热休克蛋白基因表达增强、细胞毒性功能减弱。非常规 T 细胞与其他细胞之间存在大量配体-受体对,特别是与成纤维细胞和内皮细胞。

结论

本研究绘制了 OLP 的单细胞图谱,描绘了 OLP 中非常规 T 细胞的分子特征,并揭示了这些非常规 T 细胞处于应激反应状态。

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