气候变化领域集成服务门户(CCPortal): Single-cell transcriptomic analysis reveals the immune landscape of lung in steroid-resistant asthma exacerbation

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DOI	10.1073/pnas.2005590118
	Single-cell transcriptomic analysis reveals the immune landscape of lung in steroid-resistant asthma exacerbation
	Wang L.; Netto K.G.; Zhou L.; Liu X.; Wang M.; Zhang G.; Foster P.S.; Li F.; Yang M.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	Exaggerated airway hyperresponsiveness and inflammation are hallmarks of asthma, and lipopolysaccharide (LPS) exposure is linked to the severity of the disease and steroid resistance. To investigate the mechanisms underlying asthma exacerbation, we established a mouse model of LPS-induced steroid-resistant exacerbation on the background of house dust mite (HDM)-induced asthma to profile the immune cells in lung by using single-cell RNA deep sequencing. Twenty immune subsets were identified by their molecular and functional properties. Specific cell clusters of basophils, type 2 innate lymphoid cells (ILC2), and CD8+ memory T cells were the predominant sources of interleukin (IL)-4 and IL-13 transcripts whose expressions were dexamethasone resistant. Production of IL-13 by these cells was validated by IL-13-reporter mice. Neutralization of IL-13 abolished HDM/LPS-induced airway hyperresponsiveness, airway inflammation, and decreased mucus hypersecretion. Furthermore, using Ingenuity Pathway Analysis systems, we identified canonical pathways and upstream regulators that regulate the activation of basophils, ILC2, and CD8+ memory T cells. Our study provides mechanistic insights and an important reference resource for further understanding of the immune landscape during asthma exacerbation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Asthma exacerbation; Pathway analysis; Single-cell RNA sequencing
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181075
作者单位	Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450052, China; Department of Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450052, China; Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2300, Australia; Medical Research Centre, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, 450052, China; Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, 450052, China
推荐引用方式 GB/T 7714	Wang L.,Netto K.G.,Zhou L.,et al. Single-cell transcriptomic analysis reveals the immune landscape of lung in steroid-resistant asthma exacerbation[J],2021,118(2).
APA	Wang L..,Netto K.G..,Zhou L..,Liu X..,Wang M..,...&Yang M..(2021).Single-cell transcriptomic analysis reveals the immune landscape of lung in steroid-resistant asthma exacerbation.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Wang L.,et al."Single-cell transcriptomic analysis reveals the immune landscape of lung in steroid-resistant asthma exacerbation".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).