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IL-33 expression is lower in current smokers at both transcriptomic and protein level

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Item Type:Article
Title:IL-33 expression is lower in current smokers at both transcriptomic and protein level
Creators Name:Faiz, A. and Mahbub, R.M. and Boedijono, F.S. and Tomassen, M.I. and Kooistra, W. and Timens, W. and Nawijn, M. and Hansbro, P.M. and Johansen, M.D. and Pouwels, S.D. and Heijink, I.H. and Massip, F. and de Biase, M.S. and Schwarz, R.F. and Adcock, I.M. and Chung, K.F. and van der Does, A. and Hiemstra, P.S. and Goulaouic, H. and Xing, H. and Abdulai, R. and de Rinaldis, E. and Cunoosamy, D. and Harel, S. and Lederer, D. and Nivens, M.C. and Wark, P.A. and Kerstjens, H.A.M. and Hylkema, M.N. and Brandsma, C.A. and van den Berge, M.
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.
Keywords:IL-33, Gene Expression, Cigarette Smoke, Basal Cell, COPD
Source:American Journal of Respiratory and Critical Care Medicine
Publisher:American Thoracic Society
Page Range:1075-1087
Date:15 November 2023
Official Publication:https://doi.org/10.1164/rccm.202210-1881OC
PubMed:View item in PubMed

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