circS100A11 enhances M2a macrophage activation and lung inflammation in children with asthma

Qiuyan Liang; Jinrong Fu; Xiang Wang; Lijuan Liu; Wenfeng Xiao; Yajing Gao; Lan Yang; Hongmiao Yu; Xueru Xie; Zikun Tu; Saihua Huang; Xiao Han; Liling Qian; Yufeng Zhou

doi:10.1111/all.15515

circS100A11 enhances M2a macrophage activation and lung inflammation in children with asthma

Allergy. 2023 Jun;78(6):1459-1472. doi: 10.1111/all.15515. Epub 2022 Sep 23.

Authors

Qiuyan Liang^{1

2}, Jinrong Fu^{1

3}, Xiang Wang^{1

2}, Lijuan Liu^{1

4}, Wenfeng Xiao^{1

2}, Yajing Gao^{1

2}, Lan Yang^{1

2}, Hongmiao Yu^{1

2}, Xueru Xie^{1

2}, Zikun Tu^{1

2}, Saihua Huang^{1

2}, Xiao Han^{1

2}, Liling Qian⁴, Yufeng Zhou^{1

2}

Affiliations

¹ Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
² National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China.
³ Department of General Medicine, Children's Hospital of Fudan University, Shanghai, China.
⁴ Department of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China.

PMID: 36104951
DOI: 10.1111/all.15515

Abstract

Background: Dysregulation of circRNAs is associated with a variety of human diseases; however, its role in childhood asthma is undefined.

Methods: The differential expression profiles of circRNAs were analyzed by microarray. The effects and mechanisms by which circRNAs influence macrophage activation were detected by quantitative real-time PCR, RNA immunoprecipitation assay, and chromatin immunoprecipitation assay, among others. The roles of circRNA and its host gene in asthma were tested in a cockroach allergen extract (CRE)-induced murine asthma model.

Results: We identified 372 circRNAs that were differentially expressed in PBMCs of children with asthma as compared with healthy controls. A circRNA with unknown function, circS100A11, was dominantly expressed in monocytes and significantly upregulated in children with asthma. circS100A11 facilitated M2a macrophage activation by enhancing translation of its host gene, S100A11, and exacerbated lung inflammation in a CRE-induced murine asthma model with macrophage-specific overexpression of circS100A11. Mechanistically, circS100A11 promoted S100A11 translation by competitively binding to CAPRIN1 to decrease the suppression of CAPRIN1 upon S100A11 translation. Then, S100A11 liberated SP3 from nucleolin and promoted SP3 binding to the STAT6 promoter to enhance STAT6 expression and M2a macrophage activation. Macrophage-specific knockdown of S100A11 could alleviate lung inflammation in a CRE-induced murine asthma model in vivo.

Conclusions: circS100A11 and S100A11 promote M2a macrophage activation and lung inflammation in asthma model and may serve as potential therapeutic and diagnostic targets in children with asthma.

Keywords: S100A11; asthma; children; circRNA; macrophage activation.

Publication types

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

MeSH terms

Animals
Asthma* / genetics
Cell Cycle Proteins
Child
Humans
Macrophage Activation
Mice
Pneumonia*
RNA / genetics
RNA, Circular

Substances

RNA, Circular
RNA
CAPRIN1 protein, human
Cell Cycle Proteins