Researchers have identified clusters of immune cells in the gut that appear to trigger nearby cells to produce excess collagen, the key component of scar tissue. This process, known as fibrosis, can cause sections of the intestine to narrow or become blocked over time.
Crohn’s disease is a chronic inflammatory condition of the digestive tract, and one of two forms of inflammatory bowel disease. While current treatments focus on reducing inflammation, they do little to prevent the gradual build-up of scar tissue that can permanently damage the bowel.
The team, led by the University of Edinburgh, hopes its findings will shift that focus. Their study, published in The Journal of Pathology, involved a UK-wide collaboration of researchers and clinicians.
“Fibrosis remains one of the most challenging complications of Crohn’s disease, because current treatments primarily target inflammation rather than the scarring itself,” said Dr Shahida Din, consultant gastroenterologist at NHS Lothian, and honorary senior clinical lecturer at the university.
She said understanding how immune activity drives collagen production could guide the development of therapies that slow or even prevent fibrosis.
To investigate, researchers examined intestinal tissue from Crohn’s patients, focusing on the ileum, the section of the small intestine most commonly affected. Using archived samples, they mapped structural changes across the bowel wall and found markedly higher levels of scarring and immune cell activity compared with healthy tissue.
One area stood out: the submucosa, a deeper layer of the bowel wall, where scarring was particularly pronounced. This suggests fibrosis may begin earlier and deeper than previously thought.
The team then turned to fresh tissue samples and applied single-cell RNA sequencing, a technique that allows scientists to study gene activity in individual cells.
This revealed a striking interaction: clusters of immune cells, known as Crohn’s lymphoid aggregates, were found alongside endothelial cells, which typically line blood vessels. These endothelial cells appeared to form structures around the immune clusters.
Further analysis showed that these groups were communicating with nearby collagen-producing cells, effectively encouraging the formation of scar tissue.
“Our findings highlight previously unrecognised interactions between immune cells, endothelial cells and collagen-producing cells in Crohn’s disease,” said research fellow Dr Michael Glinka.
“By combining traditional pathology with single-cell transcriptomics, we confirmed these changes through two independent approaches and identified signalling pathways that could become new therapeutic targets.”
For patients, the implications are significant. Fibrosis is one of the main reasons people with Crohn’s require surgery, yet it has remained difficult to treat directly.
Catherine Winsor, a representative from Crohn’s & Colitis UK, said the findings offer a sense of optimism. “People who live with Crohn’s often tell us how much fibrosis and scarring can affect their lives, yet it’s something current treatments don’t address,” she noted.
“This early research is exciting because it helps us understand what drives that scarring and where new treatments could make a difference. It brings real hope that, in the future, we might be able to treat not just inflammation, but the lasting damage Crohn’s can cause.”