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利用小鼠单细胞RNA测序对干眼疾病进展过程中的T细胞进行表征

Characterization of T cells in the progression of dry eye disease using single-cell RNA sequencing in mice.

作者信息

Zhang Zhizhi, Zhang Liwei, Chen Baihua

机构信息

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Hunan Clinical Research Center of Ophthalmic Disease, Changsha, 410011, Hunan, China.

出版信息

Eur J Med Res. 2025 Apr 28;30(1):338. doi: 10.1186/s40001-025-02607-2.

DOI:10.1186/s40001-025-02607-2
PMID:40296131
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12036131/
Abstract

BACKGROUND

Increasing evidence indicated that T cells have significant effects in dry eye disease (DED). However, the regulatory role of T cells in DED remains unclear.

METHODS

In this study, we examined immune responses throughout the progression in murine DED model. Using cytometry by time-of-flight (CyTOF) and single-cell RNA sequencing (scRNA-seq), we observed dynamic alterations in the proportions of immune cell landscape. Pseudotime trajectory and cell-cell communication analyses further illustrated T-cell differentiation and interaction networks.

RESULTS

CD4 and CD8 T cells exhibited an initial decline on Day 3 (D3) and followed by a recovery on Day 7 (D7). Single-cell transcriptomics provided insights into 15 distinct subsets of T cells with heterogeneous functional states. Pseudotime trajectory analysis demonstrated coordinated differentiation patterns of CD4 and CD8 T cells, indicating their collaborative involvement in the inflammatory process.

CONCLUSIONS

Our results clarify the dynamics of the adaptive immune response in DED and indicate that targeting T cells may serve as a promising immune-modulatory approach in the treatment of DED model.

摘要

背景

越来越多的证据表明,T细胞在干眼病(DED)中具有显著作用。然而,T细胞在DED中的调节作用仍不清楚。

方法

在本研究中,我们在小鼠DED模型的整个病程中检测了免疫反应。使用飞行时间细胞计数法(CyTOF)和单细胞RNA测序(scRNA-seq),我们观察了免疫细胞图谱比例的动态变化。伪时间轨迹和细胞间通讯分析进一步阐明了T细胞分化和相互作用网络。

结果

CD4和CD8 T细胞在第3天(D3)最初出现下降,随后在第7天(D7)恢复。单细胞转录组学揭示了15个具有不同功能状态的T细胞亚群。伪时间轨迹分析显示了CD4和CD8 T细胞的协同分化模式,表明它们共同参与炎症过程。

结论

我们的结果阐明了DED中适应性免疫反应的动态变化,并表明靶向T细胞可能是治疗DED模型的一种有前景的免疫调节方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d5/12036131/9a3c78efd64f/40001_2025_2607_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d5/12036131/40554c281291/40001_2025_2607_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d5/12036131/9a3c78efd64f/40001_2025_2607_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d5/12036131/40554c281291/40001_2025_2607_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d5/12036131/7f26859e6f3d/40001_2025_2607_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d5/12036131/2e8f7b85acbd/40001_2025_2607_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d5/12036131/9a3c78efd64f/40001_2025_2607_Fig7_HTML.jpg

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本文引用的文献

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Systems biology of dry eye: Unraveling molecular mechanisms through multi-omics integration.干眼的系统生物学:通过多组学整合揭示分子机制。
Ocul Surf. 2025 Apr;36:25-40. doi: 10.1016/j.jtos.2024.12.010. Epub 2024 Dec 31.
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Corneal Mucin-Targeting Liposome Nanoplatforms Enable Effective Treatment of Dry Eye Diseases by Integrated Regulation of Ferroptosis and Inflammation.角膜黏蛋白靶向脂质体纳米平台通过铁死亡和炎症的综合调节实现对干眼症的有效治疗。
Adv Sci (Weinh). 2025 Jan;12(3):e2411172. doi: 10.1002/advs.202411172. Epub 2024 Nov 28.
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CD4 T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model.
CD4 T 细胞驱动角膜神经损伤,但不引起急性水性缺乏性干眼模型中的眼表疾病。
Proc Natl Acad Sci U S A. 2024 Nov 26;121(48):e2407648121. doi: 10.1073/pnas.2407648121. Epub 2024 Nov 19.
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Linarine inhibits inflammatory responses in dry eye disease mice by modulating purinergic receptors.亚麻苦苷通过调节嘌呤能受体抑制干眼疾病小鼠的炎症反应。
Front Immunol. 2024 Sep 30;15:1463767. doi: 10.3389/fimmu.2024.1463767. eCollection 2024.
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Improvement in signs and symptoms of severe dry eye disease after dual therapy with high-potency steroids and 0.05% cyclosporine.强效能类固醇与 0.05%环孢素联合治疗重度干眼综合征后症状和体征的改善。
Ann Med. 2024 Dec;56(1):2391019. doi: 10.1080/07853890.2024.2391019. Epub 2024 Aug 19.
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Substance P regulates memory Th17 cell generation and maintenance in chronic dry eye disease.P 物质调节慢性干眼疾病中记忆性 Th17 细胞的生成和维持。
J Leukoc Biol. 2024 Nov 27;116(6):1446-1453. doi: 10.1093/jleuko/qiae142.
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Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune-Epithelial Crosstalk.基于纳米氧化铈调控免疫-上皮细胞串扰的环孢素 A 递药系统治疗干眼
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