IL-33 Expression Is Lower in Current Smokers at Both Transcriptomic and Protein Level.

Faiz, A; Mahbub, RM; Boedijono, FS; Tomassen, MI; Kooistra, W; Timens, W; Nawijn, M; Hansbro, PM; Johansen, MD; Pouwels, SD; Heijink, IH; Massip, F; de Biase, MS; Schwarz, RF; Adcock, IM; Chung, KF; van der Does, A; Hiemstra, PS; Goulaouic, H; Xing, H; Abdulai, R; de Rinaldis, E; Cunoosamy, D; Harel, S; Lederer, D; Nivens, MC; Wark, PA; Kerstjens, HAM; Hylkema, MN; Brandsma, C-A; van den Berge, M; Cambridge Lung Cancer Early Detection Programme,

IL-33 Expression Is Lower in Current Smokers at Both Transcriptomic and Protein Level.

Mahbub, RM Boedijono, FS Tomassen, MI Kooistra, W Timens, W Nawijn, M Hansbro, PM Johansen, MD Pouwels, SD Heijink, IH Massip, F de Biase, MS Schwarz, RF Adcock, IM Chung, KF van der Does, A Hiemstra, PS Goulaouic, H Xing, H Abdulai, R de Rinaldis, E Cunoosamy, D Harel, S Lederer, D Nivens, MC Wark, PA Kerstjens, HAM Hylkema, MN Brandsma, C-A van den Berge, M Cambridge Lung Cancer Early Detection Programme,

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Publisher:: American Thoracic Society
Publication Type:: Journal Article
Citation:: Am J Respir Crit Care Med, 2023
Issue Date:: 2023-09-14

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Field	Value	Language
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	Mahbub, RM
dc.contributor.author	Boedijono, FS
dc.contributor.author	Tomassen, MI
dc.contributor.author	Kooistra, W
dc.contributor.author	Timens, W
dc.contributor.author	Nawijn, M
dc.contributor.author	Hansbro, PM
dc.contributor.author	Johansen, MD
dc.contributor.author	Pouwels, SD
dc.contributor.author	Heijink, IH
dc.contributor.author	Massip, F
dc.contributor.author	de Biase, MS
dc.contributor.author	Schwarz, RF
dc.contributor.author	Adcock, IM
dc.contributor.author	Chung, KF
dc.contributor.author	van der Does, A
dc.contributor.author	Hiemstra, PS
dc.contributor.author	Goulaouic, H
dc.contributor.author	Xing, H
dc.contributor.author	Abdulai, R
dc.contributor.author	de Rinaldis, E
dc.contributor.author	Cunoosamy, D
dc.contributor.author	Harel, S
dc.contributor.author	Lederer, D
dc.contributor.author	Nivens, MC
dc.contributor.author	Wark, PA
dc.contributor.author	Kerstjens, HAM
dc.contributor.author	Hylkema, MN
dc.contributor.author	Brandsma, C-A
dc.contributor.author	van den Berge, M
dc.contributor.author	Cambridge Lung Cancer Early Detection Programme,
dc.date.accessioned	2023-09-28T01:04:41Z
dc.date.available	2023-09-28T01:04:41Z
dc.date.issued	2023-09-14
dc.identifier.citation	Am J Respir Crit Care Med, 2023
dc.identifier.issn	1073-449X
dc.identifier.issn	1535-4970
dc.identifier.uri	http://hdl.handle.net/10453/172350
dc.description.abstract	INTRODUCTION: IL-33 is a pro-inflammatory cytokine thought to play a role in the pathogenesis of asthma and COPD. A recent clinical trial using the anti-IL33 antibody showed a reduction in exacerbation and improved lung function in ex-smokers but not current smokers with COPD. In this study, we aimed to understand the effects of smoking status on IL-33. METHODS: We investigated the association of smoking status with the level of gene expression of IL33 in the airways in eight independent transcriptomic studies of lung airways. Additionally, we performed western blot and immunohistochemistry for IL-33 in lung tissue to assess protein levels. RESULTS: Across the bulk RNA-sequencing datasets, IL-33 gene expression and its signaling pathway were significantly lower in current- compared to ex- or never-smokers and increased upon smoking cessation (p<0.05). Single-cell sequencing showed that IL-33 is predominantly expressed in resting basal epithelial cells and decreases during the differentiation process triggered by smoke exposure. We also found a higher transitioning of this cellular sub-population into a more differentiated cell type during chronic smoking, potentially driving the reduction of IL-33. Protein analysis demonstrated lower IL-33 levels in lung tissue from COPD current- compared to ex-smokers and a lower proportion of IL-33 positive basal cells in current versus ex-smoking controls. CONCLUSION: We provide strong evidence that cigarette smoke leads to an overall reduction in IL33 expression in both transcriptomic and protein level and this may be due to the decrease in resting basal cells. Together, these findings may explain the clinical observation that a recent antibody-based anti-IL-33 treatment is more effective in ex- than current smokers with COPD. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.format	Print-Electronic
dc.language	eng
dc.publisher	American Thoracic Society
dc.relation	http://purl.org/au-research/grants/nhmrc/1079187
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1175134
dc.relation.ispartof	Am J Respir Crit Care Med
dc.relation.isbasedon	10.1164/rccm.202210-1881OC
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	Respiratory System
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.subject.classification	3202 Clinical sciences
dc.title	IL-33 Expression Is Lower in Current Smokers at Both Transcriptomic and Protein Level.
dc.type	Journal Article
utslib.location.activity	United States
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	closed_access	*
dc.date.updated	2023-09-28T01:04:39Z
pubs.publication-status	Published online

Abstract:

INTRODUCTION: IL-33 is a pro-inflammatory cytokine thought to play a role in the pathogenesis of asthma and COPD. A recent clinical trial using the anti-IL33 antibody showed a reduction in exacerbation and improved lung function in ex-smokers but not current smokers with COPD. In this study, we aimed to understand the effects of smoking status on IL-33. METHODS: We investigated the association of smoking status with the level of gene expression of IL33 in the airways in eight independent transcriptomic studies of lung airways. Additionally, we performed western blot and immunohistochemistry for IL-33 in lung tissue to assess protein levels. RESULTS: Across the bulk RNA-sequencing datasets, IL-33 gene expression and its signaling pathway were significantly lower in current- compared to ex- or never-smokers and increased upon smoking cessation (p<0.05). Single-cell sequencing showed that IL-33 is predominantly expressed in resting basal epithelial cells and decreases during the differentiation process triggered by smoke exposure. We also found a higher transitioning of this cellular sub-population into a more differentiated cell type during chronic smoking, potentially driving the reduction of IL-33. Protein analysis demonstrated lower IL-33 levels in lung tissue from COPD current- compared to ex-smokers and a lower proportion of IL-33 positive basal cells in current versus ex-smoking controls. CONCLUSION: We provide strong evidence that cigarette smoke leads to an overall reduction in IL33 expression in both transcriptomic and protein level and this may be due to the decrease in resting basal cells. Together, these findings may explain the clinical observation that a recent antibody-based anti-IL-33 treatment is more effective in ex- than current smokers with COPD. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/172350