Single-cell mapping of peripheral blood mononuclear cells reveals key transcriptomic changes favoring coronary artery lesion in IVIG-resistant Kawasaki disease

Yuanzheng Zheng; Yan Zhou; Di Zhu; Xing Fu; Cao Xie; Shuna Sun; Guoyou Qin; Mei Feng; Chenglong Liu; Qingtong Zhou; Fang Liu; Chen Chu; Feng Wang; Dehua Yang; Ming-Wei Wang; Yonghao Gui

Heliyon (Sep 2024)

Single-cell mapping of peripheral blood mononuclear cells reveals key transcriptomic changes favoring coronary artery lesion in IVIG-resistant Kawasaki disease

Yuanzheng Zheng,
Yan Zhou,
Di Zhu,
Xing Fu,
Cao Xie,
Shuna Sun,
Guoyou Qin,
Mei Feng,
Chenglong Liu,
Qingtong Zhou,
Fang Liu,
Chen Chu,
Feng Wang,
Dehua Yang,
Ming-Wei Wang,
Yonghao Gui

Affiliations

Yuanzheng Zheng: Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
Yan Zhou: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
Di Zhu: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
Xing Fu: Accuramed Technology (Shanghai) Ltd., Shanghai, 200233, China
Cao Xie: School of Pharmacy, Fudan University, Shanghai, 201203, China
Shuna Sun: Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
Guoyou Qin: School of Public Health, Fudan University, Shanghai, 200032, China
Mei Feng: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
Chenglong Liu: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
Qingtong Zhou: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China; Research Center for Deepsea Bioresources, Sanya, Hainan, 572025, China
Fang Liu: Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
Chen Chu: Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
Feng Wang: Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
Dehua Yang: The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; Research Center for Deepsea Bioresources, Sanya, Hainan, 572025, China
Ming-Wei Wang: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China; Research Center for Deepsea Bioresources, Sanya, Hainan, 572025, China; Department of Chemistry, School of Science, The University of Tokyo, Tokyo, 113-0033, Japan; Corresponding author. Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Yonghao Gui: Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China; Corresponding author.

Journal volume & issue: Vol. 10, no. 18
p. e37857

Abstract

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Background: Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) poses a considerable challenge to patients and their families due to its severe complications. Previous researches have highlighted the critical role of immune disorders in its pathogenesis. However, fragmented studies based on isolated cases hinder a comprehensive understanding of this deadly illness. This study aimed to explore the overall landscape of peripheral blood mononuclear cells (PBMCs) in IVIG-resistant KD patients using single-cell RNA sequencing (scRNA-seq). Methods: The scRNA-seq was used to characterize the transcriptomic profiles of IVIG-resistant KD patients, IVIG-responsive KD patients, and healthy controls. Data quality control (QC) and subsequent analysis were conducted using various R packages. These included DoubletFinder and Harmony for QC, Seurat and SingleR for identifying and annotating major cell types, ggpubr for calculating and visualizing the percentages of each cell type, Seurat for characterizing differentially expressed genes (DEGs) between groups, pheatmap for visualizing the DEGs, clusterProfiler for performing Gene Ontology (GO) enrichment analysis of DEGs, scRepertoire for TCR and BCR data analysis, Monocle for assessing cell differentiation trajectories, and CellChat for intercellular interaction evaluation. Results: High-quality single-cell transcriptome data from 12 participants were analyzed, including five with IVIG-resistant KD, four with IVIG-responsive KD, and three healthy controls. We identified 10 major cell types and observed that the differentiation of CD8+ effector T cells was impeded in IVIG-resistant KD patients with coronary artery lesion (CAL) according to cell differentiation trajectory analysis. Subsequent cell communication analysis demonstrated that myeloid cluster with high expression of LCN2, S100P, and LTF played a key role, potentially signaling through MIF-CD74/CXCR4 and MIF-CD74/CD44 ligand-receptor pairs. Conclusion: Complex immunopathological changes occur during the development of CAL in IVIG-resistant KD. Stunted differentiation of CD8+ effector T cells is noted in KD-CAL. Interactions between myeloid cells and T cells activates multiple inflammatory signaling pathways, with ligand-receptor pairs, including MIF-CD74/CXCR4 and MIF-CD74/CD44, potentially playing crucial roles.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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