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CD14单核细胞:川崎病早期血管炎症状中的免疫通讯枢纽。

CD14 monocytes: the immune communication hub in early vasculitis symptoms of Kawasaki disease.

作者信息

Song Sirui, Chen Liqin, Zhou Yuanyuan, Xu Yanbing, Li Guang, Shen Libing, Xiao Tingting, Huang Min

机构信息

Department of Cardiology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Immunol. 2025 Mar 26;16:1557231. doi: 10.3389/fimmu.2025.1557231. eCollection 2025.

DOI:10.3389/fimmu.2025.1557231
PMID:40207219
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11979218/
Abstract

BACKGROUND

Kawasaki Disease (KD) is an acute systemic vasculitis syndrome predominantly affecting children, with a propensity to induce coronary artery lesions. Aberrant immune activation and cytokines cascade reactions are involved in its pathogenesis. The aim of this study is to investigate the changes in immune cell communication during the course of KD and to identify potential biomarkers.

METHODS

The study enrolled seven pediatric patients diagnosed with Kawasaki Disease (KD) between December 2019 and December 2021. Single-cell RNA sequencing (scRNA-seq) technology was utilized to analyze peripheral blood mononuclear cells (PBMCs). Bioinformatics methods including quality control, dimensionality reduction, cell annotation, differential expression analysis, cell communication analysis, and co-expression network analysis were employed for data processing and analysis.

RESULTS

This study utilized single-cell sequencing technology to uncover the dynamics of immune cell communication during the course of KD, revealing a significant increase in the number of CD14 monocytes in the early stages of vasculitis, which play a central role in cell-cell communication. SELPLG was identified as a particularly crucial gene in the signal transduction among immune cells. The study also observed various cellular communication patterns of vasculitis at different time points and identified co-expression modules related to ribosomal function, cell proliferation, and immune responses in CD19 B cells, CD4 T cells, CD8 T cells, CD14 monocytes, and CD16 monocytes. Notably, the expression of the ITK gene in CD14 monocytes stood out. Furthermore, MHC-I genes were the most active molecules involved in signal transduction, and the expression of CD40 genes increased with the prolongation of vasculitis duration.

CONCLUSION

CD14 monocytes play a pivotal role in cellular communication during the activation process of KD vasculitis, with SELPLG and ITK as important communication signal genes. These findings provide a novel perspective for the discovery of biomarkers, prediction of disease progression, and the development of targeted treatment strategies for KD.

CLINICAL TRIAL REGISTRATION

http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=7739, identifier ChiCTR, ChiCTR2100044729.

摘要

背景

川崎病(KD)是一种主要影响儿童的急性全身性血管炎综合征,易诱发冠状动脉病变。异常的免疫激活和细胞因子级联反应参与其发病机制。本研究的目的是调查KD病程中免疫细胞通讯的变化,并确定潜在的生物标志物。

方法

本研究纳入了2019年12月至2021年12月期间诊断为川崎病(KD)的7名儿科患者。利用单细胞RNA测序(scRNA-seq)技术分析外周血单个核细胞(PBMCs)。采用包括质量控制、降维、细胞注释、差异表达分析、细胞通讯分析和共表达网络分析在内的生物信息学方法进行数据处理和分析。

结果

本研究利用单细胞测序技术揭示了KD病程中免疫细胞通讯的动态变化,发现在血管炎早期CD14单核细胞数量显著增加,其在细胞间通讯中起核心作用。SELPLG被确定为免疫细胞间信号转导中特别关键的基因。该研究还观察到不同时间点血管炎的各种细胞通讯模式,并确定了与CD19 B细胞、CD4 T细胞、CD8 T细胞、CD14单核细胞和CD16单核细胞中核糖体功能、细胞增殖和免疫反应相关的共表达模块。值得注意的是,CD14单核细胞中ITK基因的表达突出。此外,MHC-I基因是参与信号转导的最活跃分子,CD40基因的表达随血管炎病程延长而增加。

结论

CD14单核细胞在KD血管炎激活过程中的细胞通讯中起关键作用,SELPLG和ITK作为重要的通讯信号基因。这些发现为KD生物标志物的发现、疾病进展的预测以及靶向治疗策略的开发提供了新的视角。

临床试验注册

http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=7739,标识符ChiCTR,ChiCTR2100044729。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/170a/11979218/3c7e83ee24ac/fimmu-16-1557231-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/170a/11979218/1665d4af2778/fimmu-16-1557231-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/170a/11979218/9efd3b8140b0/fimmu-16-1557231-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/170a/11979218/3c7e83ee24ac/fimmu-16-1557231-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/170a/11979218/1665d4af2778/fimmu-16-1557231-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/170a/11979218/9efd3b8140b0/fimmu-16-1557231-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/170a/11979218/fa9a0a00aec5/fimmu-16-1557231-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/170a/11979218/3c7e83ee24ac/fimmu-16-1557231-g007.jpg

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Kawasaki Disease-Associated Cytokine Storm Syndrome.川崎病相关细胞因子风暴综合征。
Adv Exp Med Biol. 2024;1448:365-383. doi: 10.1007/978-3-031-59815-9_25.
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CD14 down-modulation as a real-time biomarker in Kawasaki disease.
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Clin Transl Immunology. 2023 Dec 30;13(1):e1482. doi: 10.1002/cti2.1482. eCollection 2024.
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Integration of scRNA-Seq and bulk RNA-Seq uncover perturbed immune cell types and pathways of Kawasaki disease.单细胞 RNA-Seq 和批量 RNA-Seq 的整合揭示了川崎病中失调的免疫细胞类型和途径。
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