Fibrotic Idiopathic Interstitial Lung Disease: The Molecular and Cellular Key Players

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.

Keywords: extracellular matrix proteins; idiopathic pulmonary fibrosis; lung disease; myofibroblast; tgfβ1 signalling.

Figure 1

The diagnostic and etiologic characteristic of different IIPs.

Figure 2

Molecular key players and signaling pathway characterizing the lung niche of IIP patients. Arrows indicate the molecular activation signaling leading to myofibroblasts activation and/or fibrotic disease progression process.