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Published on: March 21, 2021
Transcriptome Profiling of Induced Sputum Identified Upregulated TNF-α/NF-κB Signalling and Downregulated
Silvija P Jerkic1, Karen Naegele1, Lucia Gronau1
1Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Post-infectious bronchiolitis obliterans (PiBO) involves airway inflammation and fibrosis. Macrophage shifts and altered gene expression, including NFκB signaling, are key in PiBO pathogenesis and correlate with lung function.
Area of Science:
- Pulmonary Medicine
- Immunology
- Molecular Biology
Background:
- Post-infectious bronchiolitis obliterans (PiBO) is a chronic lung disease following severe respiratory infections.
- It is characterized by persistent inflammation and fibrotic changes in the small airways.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) in sputum cells of PiBO patients compared to healthy controls.
- To elucidate the molecular mechanisms and cellular players involved in PiBO immunopathology.
Main Methods:
- Gene expression analysis (mRNA sequencing) and multiplex immunohistochemistry (mIHC) on sputum cells.
- KEGG pathway enrichment analysis to evaluate biological targets.
- Correlation analysis between gene expression and lung function parameters (FEV1).
Main Results:
- PiBO patients exhibited reduced lung function, increased neutrophils, and altered macrophage profiles.
- Significant upregulation of TNFα-dependent NFκB signaling and downregulation of oxidative phosphorylation (OXPHOS) were observed.
- Macrophage polarization shifts were identified, correlating with DEGs and FEV1.
Conclusions:
- Macrophages play a central role in the immunopathology of PiBO.
- Altered macrophage polarization and dysregulated gene expression are key molecular mechanisms in PiBO.
- Findings enhance the understanding of PiBO's molecular basis and its impact on lung function.
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