Temporo-spatial cellular atlas of the regenerating alveolar niche in idiopathic pulmonary fibrosis
Healthy alveolar repair relies on the ability of alveolar stem cells to differentiate into specialized epithelial cells for gas exchange. In chronic fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF), this regenerative process is abnormal but the underlying mechanisms remain unclear. Here, using human lung tissue that represents different stages of disease and a 33-plex single-cell imaging mass cytometry (IMC), we present a high-resolution, temporo-spatial cell atlas of the regenerating alveolar niche. With unbiased mathematical methods which quantify statistically enriched interactions, CD206<sup>hi</sup>macrophage subtype and an alveolar basal intermediate epithelial cell emerge as the most statistically robust spatial association in the epithelial and immune cell interactome, found across all stages of disease. Spatially resolved receptor-ligand analysis further offers an in silico mechanism by which these macrophages may influence epithelial regeneration. These findings provide a foundational step toward understanding immune-epithelial dynamics in aberrant alveolar regeneration in IPF.
Authors
- Andrew Filby (ORCID: https://orcid.org/0000-0001-9078-4360)
- Praveen Weeratunga (ORCID: https://orcid.org/0000-0003-2306-0885)
- Agne Antanaviciute (ORCID: https://orcid.org/0000-0002-9019-2215)
- Lee A. Borthwick (ORCID: https://orcid.org/0000-0003-2885-3382)
- Laura Denney (ORCID: https://orcid.org/0000-0001-7082-9672)
- Colin Clelland
- Bethany Hunter (ORCID: https://orcid.org/0000-0002-9268-0511)
- Martin J. Sergeant (ORCID: https://orcid.org/0000-0001-7264-2668)
- Joshua A. Bull (ORCID: https://orcid.org/0000-0003-1475-2898)
- Andrew J. Fisher (ORCID: https://orcid.org/0000-0003-4822-7223)
- Ling‐Pei Ho (ORCID: https://orcid.org/0000-0001-8319-301X)
- James Shaw (ORCID: https://orcid.org/0000-0002-2893-3211)
- Chaitanya Vuppusetty
- Helen M. Byrne (ORCID: https://orcid.org/0000-0003-1771-5910)
- Tian Hu
- Jeongmin Woo (ORCID: https://orcid.org/0009-0001-8139-1298)
- Rachel A. Burgoyne
Institutions
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- University of Oxford (GB)
- Ludwig Cancer Research (GB)
- MRC Weatherall Institute of Molecular Medicine (GB)
- MRC Human Immunology Unit (GB)
- Science Oxford (GB)
- Weill Cornell Medical College in Qatar (QA)
- University of Newcastle Australia (AU)
- Newcastle University (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-04
- DOI
- https://doi.org/10.1038/s41467-025-61880-1
- Citations
- 1
- Primary Topic
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Type
- article
- Field-Weighted Citation Impact
- 1.52
Funders
- NHS Blood and Transplant
- National Institute for Health and Care Research
- Department of Health and Social Care
- University of Oxford
- Newcastle University
- UK Regenerative Medicine Platform
- Medical Research Council
- NIHR Oxford Biomedical Research Centre
- Medical Research Foundation