Integration of scRNA-Seq and bulk RNA-Seq uncover perturbed immune cell types and pathways of Kawasaki disease

Naixin Cao; Huayi Ouyang; Xing Zhang; Yuanyuan Xu; Jun Li; Yanfei Chen

doi:10.3389/fimmu.2023.1259353

Integration of scRNA-Seq and bulk RNA-Seq uncover perturbed immune cell types and pathways of Kawasaki disease

Front Immunol. 2023 Sep 28:14:1259353. doi: 10.3389/fimmu.2023.1259353. eCollection 2023.

Authors

Naixin Cao^{1

2}, Huayi Ouyang^{1

2}, Xing Zhang¹, Yuanyuan Xu², Jun Li², Yanfei Chen¹

Affiliations

¹ Yunnan Province Clinical Research Center for Children's Health and Disease, Kunming Children's Hospital, Kunming, China.
² Department of Immunology, Center of Immunomolecular Engineering, Innovation and Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China.

Abstract

Introduction: Kawasaki disease (KD) is an acute febrile illness primarily affecting children and characterized by systemic inflammation and vasculitis that can lead to coronary artery complications. The aim of this study was to gain a comprehensive understanding of immune dysregulation in KD.

Methods: To this end, we employed integration of single-cell RNA sequencing (scRNA-Seq) and bulk RNA sequencing (bulk RNA-Seq) data. Furthermore, we conducted flow cytometry analysis for a cohort of 82 KD patients.

Results: Our analysis revealed significant heterogeneity within immune cell populations in KD patients, with distinct clusters of T cells, B cells, and natural killer (NK) cells. Importantly, CD4⁺ naïve T cells in KD patients were found to predominantly differentiate into Treg cells and Th2 cells, potentially playing a role in the excessive inflammation and vascular damage characteristic of the disease. Dysregulated signaling pathways were also identified, including the mTOR signaling pathway, cardiomyopathy pathway, COVID-19 signaling pathway, and pathways involved in bacterial or viral infection.

Discussion: These findings provide insights into the immunopathogenesis of KD, emphasizing the importance of immune cell dysregulation and dysregulated signaling pathways. Integration of scRNA-Seq and bulk RNA-Seq data offers a comprehensive view of the molecular and cellular alterations in KD and highlights potential therapeutic targets for further investigation. Validation and functional studies are warranted to elucidate the roles of the identified immune cell types and pathways in KD pathogenesis and to develop targeted interventions to improve patient outcomes.

Keywords: KD; ScRNA-seq; WGCNA; immune dysregulation; immunopathogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Child
Coronary Vessels
Humans
Inflammation
Mucocutaneous Lymph Node Syndrome* / genetics
RNA-Seq
Single-Cell Gene Expression Analysis

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Foundation of Yunnan Province Clinical Research Center for Children’s Health and Disease (2022-ETYY-YJ-16) and Science Research Foundation of Yunnan Provincial Department of Education (2023J0298).