Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics

Jones, Anya C., Troy, Niamh M., White, Elisha, Hollams, Elysia M., Gout, Alexander M., Ling, Kak-Ming, Kicic, Anthony, Stick, Stephen M., Sly, Peter D., Holt, Patrick G., Hall, Graham L. and Bosco, Anthony (2018) Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics. Scientific Reports, 8 1: 1511. doi:10.1038/s41598-018-19837-6


Author Jones, Anya C.
Troy, Niamh M.
White, Elisha
Hollams, Elysia M.
Gout, Alexander M.
Ling, Kak-Ming
Kicic, Anthony
Stick, Stephen M.
Sly, Peter D.
Holt, Patrick G.
Hall, Graham L.
Bosco, Anthony
Title Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2018-01-24
Year available 2018
Sub-type Article (original research)
DOI 10.1038/s41598-018-19837-6
Open Access Status DOI
Volume 8
Issue 1
Start page 1511
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Atopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDMS) subjects with/ without wheezing history that are characteristic of the ongoing asthmatic state. The expression of type 2 effectors (IL-5, IL-13) was equivalent in both cohorts of subjects. However, in HDMS-wheezers they were associated with upregulation of two coexpression modules comprising multiple type 2-and epithelial-associated genes. The first module was interlinked by the hubs EGFR, ERBB2, CDH1 and IL-13. The second module was associated with CDHR3 and mucociliary clearance genes. Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatics undergoing natural aeroallergen exposure, and suggest that susceptibility to asthma amongst these subjects involves complex interactions between type 2-and epithelial-associated gene networks, which are not operative in equivalently sensitized/exposed atopic non-asthmatics.
Formatted abstract
Atopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDMS) subjects with/without wheezing history that are characteristic of the ongoing asthmatic state. The expression of type 2 effectors (IL-5, IL-13) was equivalent in both cohorts of subjects. However, in HDMS-wheezers they were associated with upregulation of two coexpression modules comprising multiple type 2- and epithelial-associated genes. The first module was interlinked by the hubs EGFR, ERBB2, CDH1 and IL-13. The second module was associated with CDHR3 and mucociliary clearance genes. Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatics undergoing natural aeroallergen exposure, and suggest that susceptibility to asthma amongst these subjects involves complex interactions between type 2- and epithelial-associated gene networks, which are not operative in equivalently sensitized/exposed atopic non-asthmatics.
Keyword Growth-Factor Receptor
Chronic Lung-Disease
Allergic Sensitization
Severe Exacerbations
Pathway Analysis
Inflammation
Expression
Phenotypes
Differentiation
Deficiency
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1027449
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Child Health Research Centre Publications
 
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Created: Wed, 31 Jan 2018, 12:09:59 EST