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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ac16e7684d348ea85dff8c594b24574
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spelling	oai:doaj.org-article:3ac16e7684d348ea85dff8c594b245742021-12-02T15:09:08ZPersistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics10.1038/s41598-018-19837-62045-2322https://doaj.org/article/3ac16e7684d348ea85dff8c594b245742018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19837-6https://doaj.org/toc/2045-2322Abstract 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.Anya C. JonesNiamh M. TroyElisha WhiteElysia M. HollamsAlexander M. GoutKak-Ming LingAnthony KicicStephen M. StickPeter D. SlyPatrick G. HoltGraham L. HallAnthony BoscoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
description	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.
format	article
author	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
author_facet	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
author_sort	Anya C. Jones
title	Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
title_short	Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
title_full	Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
title_fullStr	Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
title_full_unstemmed	Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
title_sort	persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3ac16e7684d348ea85dff8c594b24574
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Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics

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