- Title
- Single-cell transcriptomic analysis reveals the immune landscape of lung in steroid-resistant asthma exacerbation
- Creator
- Wang, Lingli; Netto, Keilah G.; Zhou, Lujia; Liu, Xiaojie; Wang, Ming; Zhang, Guojun; Foster, Paul S.; Li, Fuguang; Yang, Ming
- Relation
- National Academy of Sciences. Proceedings Vol. 118, Issue 2, no. e2005590118
- Publisher Link
- http://dx.doi.org/10.1073/pnas.2005590118
- Publisher
- National Academy of Sciences
- Resource Type
- journal article
- Date
- 2021
- Description
- 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.
- Subject
- single-cell RNA sequencing; asthma exacerbation; pathway analysis; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1468151
- Identifier
- uon:48011
- Identifier
- ISSN:0027-8424
- Language
- eng
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