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Researchers at the MRC Translational Immune Discovery Unit, in collaboration with colleagues at Newcastle University, have developed the first mathematically supported cellular map of lung tissue in idiopathic pulmonary fibrosis (IPF), a deadly lung disease with no known cure. The findings, published in Nature Communications, reveal a specific interaction between immune and epithelial cells that could be driving the disease, opening the door to new treatment approaches.
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, led by Professor Ling-Pei Ho, 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 Ho 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.
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.
“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,” said Praveen Weeratunga, first author of the study. “This could help guide the development of treatments aimed at restoring healthy lung repair.”
“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”, added Professor Ho.
Read the full paper here: Temporo-spatial cellular atlas of the regenerating alveolar niche in idiopathic pulmonary fibrosis