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Lookup NU author(s): Bethany Hunter, Rachel Burgoyne, Dr Lee BorthwickORCiD, Professor James ShawORCiD, Professor Andrew FilbyORCiD, Professor Andrew FisherORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2025. 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, CD206himacrophage 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.
Author(s): Weeratunga P, Hunter B, Sergeant M, Bull J, Clelland C, Denney L, Vuppusetty C, Burgoyne R, Woo J, Hu T, Borthwick L, Shaw J, Antanaviciute A, Filby A, Byrne H, Fisher A, Ho L-P
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2025
Volume: 16
Online publication date: 04/08/2025
Acceptance date: 03/07/2025
Date deposited: 01/10/2025
ISSN (electronic): 2041-1723
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41467-025-61880-1
DOI: 10.1038/s41467-025-61880-1
Data Access Statement: The spatial mass cytometry data files (MCD) generated in this study have been deposited in the Zenodo database under accession code 10930946 (https://doi.org/10.5281/zenodo.10930946). The processed source data used in the analyses presented in the paper is available for download as an online resource in Multi-Dimensional Viewer (MDV) accessible with the hyperlink, (https://mdv.molbiol.ox.ac.uk/projects/mdv_project/7430). Specific source data for graphs are also provided in the source data file. Source data are provided with this paper.
PubMed id: 40759629
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