Abstract
Interstitial lung diseases (ILDs) that are known as diffuse parenchymal lung diseases (DPLDs) lead to the damage of alveolar epithelium and lung parenchyma, culminating in inflammation and widespread fibrosis. ILDs that account for more than 200 different pathologies can be divided into two groups: ILDs that have a known cause and those where the cause is unknown, classified as idiopathic interstitial pneumonia (IIP). IIPs include idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) known also as bronchiolitis obliterans organizing pneumonia (BOOP), acute interstitial pneumonia (AIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and lymphocytic interstitial pneumonia (LIP). In this review, our aim is to describe the pathogenic mechanisms that lead to the onset and progression of the different IIPs, starting from IPF as the most studied, in order to find both the common and standalone molecular and cellular key players among them. Finally, a deeper molecular and cellular characterization of different interstitial lung diseases without a known cause would contribute to giving a more accurate diagnosis to the patients, which would translate to a more effective treatment decision.
Highlights
Interstitial lung diseases (ILDs) are a heterogeneous group of pathologies that affect the lung parenchyma with wide inflammation and diffuse fibrosis [1]
We found the following: interstitial lung fibroblasts localized in the interstitium immediately adjacent to alveolar epithelial cells [33], lipofibroblasts located near the AECs are lipid-droplet-containing interstitial fibroblasts [35], pericytes within the capillary basement membrane [36], mesothelial cells from pleural-mesothelium that line the visceral and parietal pleural surfaces [37], and resident lung mesenchymal progenitors, whose contribution in the myofibroblastdifferentiating process seems prevalent [38]
Idiopathic pulmonary fibrosis—idiopathic pulmonary fibrosis (IPF)—In normal lungs, when alveolar injuries occur there is a depletion of alveolar epithelial cells 1 (AECI) located at the interface, with vascular endothelium participating in alveolar gas exchange functions
Summary
Interstitial lung diseases (ILDs) are a heterogeneous group of pathologies that affect the lung parenchyma with wide inflammation and diffuse fibrosis [1]. Idiopathic pulmonary fibrosis represents the most common form of idiopathic interstitial pneumonia (IIP) and is characterized by the progressive remodeling of the lung parenchyma structure, which exaggerates extracellular matrix deposition and irreversible scarring. According to the current integral model, the fibrotic pathway in IPF patients is activated by recurrent alveolar epithelium injury (e.g., environmental risks) that, together with compromised repair mechanisms of alveolar epithelium, leads to the initiation, development and progression of the disease [24,25,26]. The alveolar epithelial cells (AECs) are unable to properly respond to repetitive injuries, resulting in the loss of epithelial integrity that, together with the secretion of pro-fibrotic factors, represents the initial crucial mechanism of IPF development promoting fibroblast migration, proliferation, activation and differentiation into myofibroblasts with deposition of Extracellular Matrix (ECM) and the following distortion of the lung architecture. The identification of multiple mechanisms behind the proliferation of resident fibroblasts, the transdifferentiation of the above-mentioned cellular type in myofibroblasts and the aberrant deposition of the extracellular matrix in the fibrotic lungs could be crucial for the identification of new therapies that would be able to reverse the pathological mechanisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
