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

Anya C. Jones, Niamh M. Troy, Elisha White, Elysia M. Hollams, Alexander M. Gout, Kak Ming Ling, Anthony Kicic, Stephen M. Stick, Peter D. Sly, Patrick G. Holt, Graham L. Hall, Anthony Bosco

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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.

LanguageEnglish
Article number1511
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2018

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Gene Regulatory Networks
Sputum
Asthma
Interleukin-13
Mucociliary Clearance
Pyroglyphidae
Interleukin-5
Respiratory Sounds
Genes
Immunity
Mucous Membrane
Up-Regulation
RNA
Inflammation
Lung

Cite this

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title = "Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics",
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.",
author = "Jones, {Anya C.} and Troy, {Niamh M.} and Elisha White and Hollams, {Elysia M.} and Gout, {Alexander M.} and Ling, {Kak Ming} and Anthony Kicic and Stick, {Stephen M.} and Sly, {Peter D.} and Holt, {Patrick G.} and Hall, {Graham L.} and Anthony Bosco",
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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.; Bosco, Anthony.

In: Scientific Reports, Vol. 8, No. 1, 1511, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Jones,Anya C.

AU - Troy,Niamh M.

AU - White,Elisha

AU - Hollams,Elysia M.

AU - Gout,Alexander M.

AU - Ling,Kak Ming

AU - Kicic,Anthony

AU - Stick,Stephen M.

AU - Sly,Peter D.

AU - Holt,Patrick G.

AU - Hall,Graham L.

AU - Bosco,Anthony

PY - 2018/12/1

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