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Transcriptome profiling of induced sputum identified upregulated TNF-α/NF-κB signalling and downregulated mitochondrial respiratory chain function in post-infectious bronchiolitis obliterans

Post-infectious bronchiolitis obliterans (PiBO) is a chronic lung disease that develops after severe lower respiratory infections and leads to persistent inflammation and fibrotic changes in the small airways. In the present study, gene expression analysis was used to identify differentially express...

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Main Authors: Jerkic, Silvija P. (Author) , Naegele, Karen (Author) , Gronau, Lucia (Author) , Detring, Annika (Author) , Trischler, Jordis (Author) , Blümchen, Katharina (Author) , Rotter, Björn (Author) , Alkhatib, Mohammed (Author) , Mijatovic, Margarete (Author) , Weigert, Andreas (Author) , Chiocchetti, Andreas G. (Author) , Zielen, Stefan (Author) , Schubert, Ralf (Author)
Format: Article (Journal)
Language:English
Published: 19 May 2026
In: Biomolecules
Year: 2026, Volume: 16, Issue: 5, Pages: 1-21
ISSN:2218-273X
DOI:10.3390/biom16050745
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/biom16050745
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2218-273X/16/5/745
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Author Notes:Silvija P. Jerkic, Karen Naegele, Lucia Gronau, Annika Detring, Jordis Trischler, Katharina Blümchen, Björn Rotter, Mohammed Alkhatib, Margarete Mijatovic, Andreas Weigert, Andreas G. Chiocchetti, Stefan Zielen and Ralf Schubert
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Summary:Post-infectious bronchiolitis obliterans (PiBO) is a chronic lung disease that develops after severe lower respiratory infections and leads to persistent inflammation and fibrotic changes in the small airways. In the present study, gene expression analysis was used to identify differentially expressed genes (DEGs) in sputum cells derived from PiBO patients and compare them to healthy controls. Clinical history, lung function parameters, and induced sputum samples were collected from nine patients with PiBO and eight healthy controls. Multiplex immunohistochemistry (mIHC) as well as mRNA sequencing (MACE-Seq) were performed. Evaluation of the biological targets was done by KEGG pathway enrichment analysis. PiBO patients showed significantly reduced lung function parameters, an increased neutrophil count, and an altered macrophage profile in sputum. Transcriptome analysis revealed significant upregulation of the TNFα-dependent NFκB signalling pathway, as well as significant downregulation of the oxidative phosphorylation (OXPHOS). Linear regression analyses and mIHC indicated a shift in macrophage polarisation that may contribute to the dysregulated gene expression. Notably, expression of these DEGs significantly correlated with FEV1 lung function. These findings indicate a central role of macrophages in the immunopathology of PiBO and contribute to our understanding of the molecular mechanisms involved in the disease process.
Item Description:Gesehen am 13.07.2026
Physical Description:Online Resource
ISSN:2218-273X
DOI:10.3390/biom16050745

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