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Cell-Surface Programmed Death Ligand-1 Expression Identifies a Sub-Population of Distal Epithelial Cells Enriched in Idiopathic Pulmonary Fibrosis
 
 
Review

Regeneration or Repair? The Role of Alveolar Epithelial Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF)

1
Pulmonology Department, Cattinara Hospital, University of Trieste, 34127 Trieste, Italy
2
Department of Medical Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy
3
Functional Cell Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy
4
Life Sciences Department, University of Trieste, 34128 Trieste, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: C Arnold Spek
Cells 2022, 11(13), 2095; https://doi.org/10.3390/cells11132095
Received: 20 May 2022 / Revised: 26 June 2022 / Accepted: 29 June 2022 / Published: 30 June 2022
(This article belongs to the Special Issue Epithelial Cells Role in Lung Diseases)
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) with unknown etiology in which gradual fibrotic scarring of the lungs leads to usual interstitial pneumonia (UIP) and, ultimately, to death. IPF affects three million people worldwide, and the only currently available treatments include the antifibrotic drugs nintedanib and pirfenidone, which effectively reduce fibrosis progression are, unfortunately, not effective in curing the disease. In recent years, the paradigm of IPF pathogenesis has shifted from a fibroblast-driven disease to an epithelium-driven disease, wherein, upon recurrent microinjuries, dysfunctional alveolar type II epithelial cells (ATII) are not only unable to sustain physiological lung regeneration but also promote aberrant epithelial–mesenchymal crosstalk. This creates a drift towards fibrosis rather than regeneration. In the context of this review article, we discuss the most relevant mechanisms involved in IPF pathogenesis with a specific focus on the role of dysfunctional ATII cells in promoting disease progression. In particular, we summarize the main causes of ATII cell dysfunction, such as aging, environmental factors, and genetic determinants. Next, we describe the known mechanisms of physiological lung regeneration by drawing a parallel between embryonic lung development and the known pathways involved in ATII-driven alveolar re-epithelization after injury. Finally, we review the most relevant interventional clinical trials performed in the last 20 years with the aim of underlining the urgency of developing new therapies against IPF that are not only aimed at reducing disease progression by hampering ECM deposition but also boost the physiological processes of ATII-driven alveolar regeneration. View Full-Text
Keywords: IPF; ATII cells; regeneration; senescence IPF; ATII cells; regeneration; senescence
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MDPI and ACS Style

Confalonieri, P.; Volpe, M.C.; Jacob, J.; Maiocchi, S.; Salton, F.; Ruaro, B.; Confalonieri, M.; Braga, L. Regeneration or Repair? The Role of Alveolar Epithelial Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Cells 2022, 11, 2095. https://doi.org/10.3390/cells11132095

AMA Style

Confalonieri P, Volpe MC, Jacob J, Maiocchi S, Salton F, Ruaro B, Confalonieri M, Braga L. Regeneration or Repair? The Role of Alveolar Epithelial Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Cells. 2022; 11(13):2095. https://doi.org/10.3390/cells11132095

Chicago/Turabian Style

Confalonieri, Paola, Maria Concetta Volpe, Justin Jacob, Serena Maiocchi, Francesco Salton, Barbara Ruaro, Marco Confalonieri, and Luca Braga. 2022. "Regeneration or Repair? The Role of Alveolar Epithelial Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF)" Cells 11, no. 13: 2095. https://doi.org/10.3390/cells11132095

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