The study by researchers at NDM’s Respiratory Medicine Unit and the MRC Translational Immune Discovery Unit, in collaboration with Newcastle University and supported by the NIHR Oxford Biomedical Research Centre, reveal a critical interaction between immune and epithelial cells that could be driving the disease — and open the door to new treatment approaches.
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive condition in which scarring builds up in the lungs, making it increasingly difficult to breathe. Although current medications can slow its progression, they do not stop or reverse the damage.
For years, scientists have known that abnormal healing processes contribute to the disease. However, the exact cellular players and how they interact in the lungs remained largely unclear.
Using advanced imaging technology and computational analysis, the research team created a high-resolution ‘cellular atlas’ of lung tissue donated by IPF patients who were undergoing lung transplantation. The atlas captures both the identity and location of immune and structural cells in diseased lung tissue across different stages of the disease.
Professor Ling-Pei Ho, Professor of Respiratory Immunology at NDM and study lead, said: ‘We’ve taken lung tissue samples and looked at them in an entirely new way — not just identifying the cell types present, but mapping where they are in relation to each other. This allows us to understand how certain immune cells may be influencing abnormal lung repair.’
Professor Ho, is also affiliated with the MRC Weatherall Institute for Molecular Medicine and is the Oxford Biomedical Research Centre’s Theme Lead for Respirator Medicine.
Images showing CD206hi alveolar macrophages (arrows) in the alveolar space of lungs affected by fibrosis, using a microscope (A), mass cytometry (B) and lung section after computational analysis to determine the identity of each cell.
A major finding from the study was the discovery of a highly specific spatial link between two cell types: a damaged epithelial cell known as an aberrant basal intermediate (ABI) and a distinct immune cell called the CD206hi macrophage. These macrophages were the only immune cells found to spatially associate with ABIs at all stages of the disease.
Further analysis showed that the two cell types communicate through specific molecular signals — suggesting they may work together in a way that reinforces scarring and prevents proper lung regeneration.
Praveen Weeratunga, first author of the study, said: ‘By combining spatial analysis, single-cell RNA sequencing, and protein profiling, we were able to pinpoint the immune cells that may be actively driving the faulty repair process in IPF lungs. This could help guide the development of treatments aimed at restoring healthy lung repair.’
Professor Ho added: ‘This study highlights the power of interdisciplinary research, bringing together experts in IPF and lung diseases, cellular imaging, immunology, pathology, computational biology and mathematics to tackle one of the most complex and challenging diseases in respiratory medicine.’
Read the full paper on the Nature Communications website: https://www.nature.com/articles/s41467-025-61880-1?utm_source=rct_congratemailt&utm_medium=email&utm_campaign=oa_20250804&utm_content=10.1038/s41467-025-61880-1