Targeting the epithelium in pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is characterised by progressive scarring primarily of the distal regions of the lung in a distinctive histological pattern. Consequently, drug discovery has focused on the activity of scar-forming fibroblasts, with some success shown by the pharmaceutical agents nintedanib and pirfenidone, and more recently nerandomilast. Yet an unmet medical need remains, pointing toward pathobiology not addressed by standard-of-care therapies. In recent years, single-cell sequencing of patient lung tissue has revealed several novel disease-associated epithelial populations. In addition, we are now beginning to understand, through functional co-culture studies, the importance of cellular crosstalk in both lung homeostasis and disease. Here, we review the advances made in "omic" technologies, the approaching spatial profiling revolution, current and future functional cell systems, novel <i>in vivo</i> models, how we assign disease-relevance to test systems <i>via</i> computational gene set enrichment analysis, and link all these elements to clinically relevant biomarkers. We show how epithelial populations, identified and validated through cutting-edge technologies, may provide targets for the next wave of therapeutics for patients with IPF.
Authors
- Jonathan A. Kropski (ORCID: https://orcid.org/0000-0002-8923-1344)
- Irina Shalashova (ORCID: https://orcid.org/0000-0001-9914-9574)
- Jason J. Gokey (ORCID: https://orcid.org/0000-0001-8244-7831)
- Felix Wolf (ORCID: https://orcid.org/0000-0001-6595-3599)
- Muriel Lizé (ORCID: https://orcid.org/0000-0002-4954-3503)
- Anna Engler (ORCID: https://orcid.org/0000-0002-2992-5512)
- Ralf Heilker (ORCID: https://orcid.org/0000-0002-8037-2052)
- Holger Schlüter (ORCID: https://orcid.org/0000-0002-8238-564X)
- Heiko Stahl
- Stephan Klee (ORCID: https://orcid.org/0000-0003-3905-1596)
- Marina Bleck (ORCID: https://orcid.org/0000-0003-4175-8363)
- Christian T. Wohnhaas (ORCID: https://orcid.org/0000-0002-1450-9284)
- Heiko Olbrich (ORCID: https://orcid.org/0000-0002-0176-0728)
- Timothy S. Blackwell (ORCID: https://orcid.org/0000-0002-0337-7052)
- Lutz Wollin (ORCID: https://orcid.org/0000-0002-3617-5772)
- Christoph H. Mayr (ORCID: https://orcid.org/0000-0001-5353-4768)
- Alexander C. Klimowicz
- Devona Soetopo
- Marie‐Therese Bammert (ORCID: https://orcid.org/0009-0003-2368-4409)
- Matthew J. Thomas
- Kerstin Geillinger-Kästle
- A. Scott McCall
Institutions
- Boehringer Ingelheim (Germany) (DE)
- Vanderbilt University (US)
- University of Michigan (US)
- Boehringer Ingelheim (France) (FR)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- European Respiratory Review
- Published
- 2026-01-01
- DOI
- https://doi.org/10.1183/16000617.0225-2025
- Primary Topic
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Type
- article
- Field-Weighted Citation Impact
- 0.00