They found clusters of immune cells in the gut which may be stimulating nearby cells to generate excess scar tissue, known as fibrosis.
The discovery could help pinpoint new therapeutic targets to prevent or slow the development of fibrosis, a serious complication of Crohn’s disease, experts say.
Scar tissue
Crohn’s disease is a chronic inflammatory condition affecting the digestive tract. Over time, ongoing inflammation can lead to fibrosis, where excess collagen builds up in the bowel wall. This scarring can cause the intestine to narrow and become blocked, requiring surgery.
Despite affecting one in five patients with Crohn’s disease, the biological processes that trigger fibrosis remain poorly understood. Current treatments primarily target inflammation rather than the scarring itself.
The University of Edinburgh-led research team analysed intestinal tissue samples from Crohn’s disease patients with fibrosis, focusing on the ileum – the final part of the small intestine where the disease most commonly develops.
They used archived intestinal tissue samples to examine structural changes across the different layers of the bowel wall.
They found significantly increased fibrosis and immune cell infiltration in Crohn’s disease tissue compared with normal tissue. The submucosa – a deeper layer of the bowel wall – had particularly high levels of scarring, indicating it may play an important role in the early stages of fibrosis.
Cell clusters
Researchers next analysed fresh intestinal tissue samples using a cutting-edge technique to study gene activity in individual cells, known as single-cell RNA sequencing.
They identified a link between clusters of immune cells – known as Crohn’s lymphoid aggregates – and groups of endothelial cells, which normally line blood vessels. The endothelial cells appeared to form distinctive structures surrounding the Crohn’s lymphoid aggregates.
Further analysis revealed signalling interactions between these clusters and nearby cells responsible for producing collagen, suggesting that they may actively promote fibrosis.
The research highlights potential therapeutic targets that could be explored to interrupt the scarring process and develop treatments specifically aimed at fibrosis in Crohn’s disease, experts say.