Idiopathic pulmonary fibrosis microenvironment: Novel mechanisms and research directions

• Published in: International immunopharmacology Vol. 155; p. 114653
• Main Authors: Gao, Fuguo, Pan, Lei, Liu, Wei, Chen, Jian, Wang, Yifeng, Li, Yan, Liu, Yurou, Hua, Yiying, Li, Ruiqi, Zhang, Tongtong, Zhu, Ting, Jin, Faguang, Gao, Yongheng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 16.05.2025
• Subjects: Animals; Cellular Microenvironment; Extracellular Vesicles; Humans; Idiopathic pulmonary fibrosis; Idiopathic Pulmonary Fibrosis - immunology; Idiopathic Pulmonary Fibrosis - pathology; Idiopathic Pulmonary Fibrosis - therapy; Lung - immunology; Lung - microbiology; Lung - pathology; Lung microbiota; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Microenvironment; Signal Transduction; Signaling pathways; Stem cells; AT I; BLM; miRNAs; Idiopathic pulmonary fibrosis; Extracellular vesicles; Microenvironment; JAK/STAT; LPS; CTGF; Signaling pathways; iPSCs; NF-κB; MSCs; ADMSCs; PI3K; Nrf2; AT II; mTOR; EndMT; Lung microbiota; EVs; UCMSCs; VEGF; Treg; AECs; EMT; SCFA; ECM; Stem cells; ROS; TLR4; BMSCs; IPF
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2025.114653

Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease marked by increasing dyspnea and respiratory failure. The underlying mechanisms remain poorly understood, given the complexity of its pathogenesis. This review investigates the microenvironment of IPF to identify novel mechanisms and therapeutic avenues. Studies have revealed that various cell types, including alveolar epithelial cells, fibroblasts, myofibroblasts, and immune cells, are integral to disease progression, engaging in cellular stress responses and inflammatory regulation via signaling pathways such as TGF-β, Wnt, mTOR, and ROS. Non-coding RNAs, particularly miRNAs, are critical in IPF and may serve as diagnostic and prognostic biomarkers. Regarding treatment, mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) or non-vesicular derivatives offer promise by modulating immune responses, enhancing tissue repair, and inhibiting fibrosis. Additionally, alterations in the lung microbiota are increasingly recognized as a contributing factor to IPF progression, offering fresh insights into potential treatments. Despite the encouraging results of MSC-based therapies, the precise mechanisms and clinical applications remain subjects of ongoing research. This review emphasizes the significance of the IPF microenvironment and highlights the need for further exploration to develop effective therapies that could enhance patient outcomes. •This review explores the complex microenvironment of IPF, highlighting novel mechanisms and therapeutic opportunities.•Multiple cell types drive IPF pathogenesis via signaling pathways, including TGF-β, Wnt, mTOR, and ROS.•Non-coding RNAs (e.g., miRNAs) critically regulate IPF progression and serve as potential diagnostic/prognostic biomarkers.•MSCs and MSCs-EVs can treat IPF by modulating immune responses, enhancing tissue repair, and suppressing fibrosis.•Dysbiosis of the lung microbiome is linked to IPF progression, providing novel avenues for therapeutic intervention.