Transcriptomic and Network Analysis Identifies Shared and Unique Pathways and Immune Changes Across Fibrotic Interstitial Lung Diseases.
Aging(2024)
Abstract
BACKGROUND:Interstitial lung disease (ILD) encompasses a diverse group of disorders characterized by chronic inflammation and fibrosis of the pulmonary interstitium. Three ILDs, namely idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (fHP), and connective tissue disease-associated ILD (CTD-ILD), exhibit similar progressive fibrosis phenotypes, yet possess distinct etiologies, encouraging us to explore their different underlying mechanisms. METHODS:Transcriptome data of fibrotic lung tissues from patients with IPF, fHP, and CTD-ILD were subjected to functional annotation, network, and pathway analyses. Additionally, we employed the xCell deconvolution algorithm to predict immune cell infiltration in patients with fibrotic ILDs and healthy controls. RESULTS:We identified a shared progressive fibrosis-related module in these diseases which was related to extracellular matrix (ECM) degradation and production and potentially regulated by the p53 family transcription factors. In IPF, neuron-related processes emerged as a critical specific mechanism in functional enrichment. In fHP, we observed that B cell signaling and immunoglobulin A (IgA) production may act as predominant processes, which was further verified by B cell infiltration and the central role of CD19 gene. In CTD-ILD, active chemokine processes were enriched, and active dendritic cells (aDCs) were predicted to infiltrate the lung tissues. CONCLUSIONS:This study revealed shared and specific molecular and cellular pathways among IPF, fHP, and CTD-ILD, providing a basis for understanding their pathogenesis and identifying potential therapeutic targets.
MoreTranslated text
Key words
fibrotic interstitial lung diseases,idiopathic pulmonary fibrosis,fibrotic hypersensitivity pneumonitis,connective tissue disease-associated interstitial lung diseases,transcriptome data
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined