Inside the immune ‘handbook’ set to disrupt fibrosis research

A team of researchers from Duke-NUS Medical School has assembled what they call a scientific ‘handbook’ to guide future breakthroughs in fibrosis research. Published in Nature Reviews Immunology, the review consolidates insights from more than 200 studies, offering a clear picture of how specific immune cells contribute to harmful scarring in vital organs.

Zooming in on fibrosis with single-cell precision

Fibrosis, or excessive tissue scarring, is a common feature of chronic diseases that affect the lungs, kidneys, heart and liver. Fibrosis impacts nearly a billion people globally, yet efforts to develop effective treatments have been hampered by the complexity of the disease.

That complexity is now being tackled with sophisticated single-cell technologies. These tools allow scientists to isolate and study individual cells, revealing how different immune cell types behave in specific tissues over time.

The review, led by Associate Professor Jacques Behmoaras from Duke-NUS’ Cardiovascular and Metabolic Disorders Programme, spotlights macrophages as central players in the fibrotic process.

“Think of macrophages as having ‘happy’ faces, promoting healthy tissue repair, or ‘angry’ faces, causing harmful scarring,” said Behmoaras. “Recent technological advances have made it possible to identify exactly which cells trigger fibrosis, opening new doors for targeted treatments.”

Using single-cell RNA sequencing, researchers have mapped how macrophages change their characteristics depending on their environment. For instance, lung macrophages express the PPARG gene, while those in the kidneys show CD81.

A particularly harmful subset of these cells, known as SPP1+ macrophages, has been linked to fibrosis in multiple organs. These ‘troublemakers’ display specific markers such as SPP1, TREM2 and CD9, and were a focus of earlier work by the Duke-NUS team in identifying a potential “scar code”.

Targeting fibrosis at the source

Another key finding from the review highlights how macrophages interact with fibroblasts – the cells responsible for producing collagen during tissue repair. Normally, this partnership helps maintain healthy organ function. However when SPP1+ macrophages dominate, they send signals that cause fibroblasts to overproduce scar tissue, tipping the balance toward disease.

Importantly, these insights offer new therapeutic possibilities. By targeting the unique markers or signals used by SPP1+ macrophages, or by blocking their communication with fibroblasts, researchers hope to slow or even reverse fibrosis.

“As we continue making significant progress in fibrosis research, we wanted to create a clear and accessible resource – a ‘handbook’ – to guide translational researchers globally,” said Professor Enrico Petretto, systems geneticist and Director of the Duke-NUS Centre for Computational Biology.

“Our aim is to accelerate discoveries, foster new ideas and ultimately transform treatment for millions affected by fibrosis.”

The team’s efforts mark a turning point in the search for precision therapies. With this resource now available, researchers worldwide have a powerful tool to better understand and combat one of the most stubborn complications of chronic disease.

The full review is available in  Nature Reviews Immunology.