Crohn's Scarring Trigger Identified, Study Finds
LONDON, April 6 (Bernama-PA Media/dpa) -- Research suggests that scientists have identified what drives the development of scar tissue in the intestines of people with Crohn's disease, reported PA Media/dpa.
Scientists found clusters of immune cells in the gut that may stimulate nearby cells to generate excess scar tissue, known as fibrosis.
It is hoped that the discovery, detailed in a new study, could help develop treatments to prevent or slow the development of fibrosis, a serious complication of Crohn's disease.
Crohn’s is a long-term, inflammatory condition affecting the digestive tract, and, 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, meaning that surgery may be required.
The University of Edinburgh-led research team hopes the latest findings could help pinpoint therapeutic targets to interrupt the scarring process and develop treatments specifically aimed at fibrosis.
Shahida Din, consultant gastroenterologist at NHS Lothian and honorary senior clinical lecturer at the University of Edinburgh, said: "Fibrosis remains one of the most challenging complications of Crohn's disease because current treatments primarily target inflammation rather than the scarring itself."
"Understanding the cellular signalling pathways that link immune activity to collagen production could help guide the development of therapies aimed at preventing or slowing fibrosis."
The research team analysed intestinal tissue samples from patients with Crohn's disease and fibrosis, focusing on the ileum – the final part of the small intestine where the disease most commonly develops.
The researchers 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 – showed particularly high levels of scarring, indicating that it may play an important role in the early stages of fibrosis.
Researchers then 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, called Crohn’s lymphoid aggregates, and groups of endothelial cells, which normally line blood vessels.
Scientists found that 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.
Michael Glinka, research fellow at the University of Edinburgh, said: "Our findings highlight previously unrecognised interactions between immune cells, endothelial cells and collagen-producing cells in Crohn's disease."
"By combining traditional pathology with single-cell transcriptomics, we were able to confirm these changes using two independent approaches and uncover biological signalling pathways that may provide new therapeutic targets."
The research was published in The Journal of Pathology.
It was conducted by a United Kingdom (UK)-wide collaboration of researchers and clinicians and supported by funding from the Leona M. and Harry B. Helmsley Charitable Trust.
Catherine Winsor, Director of Service, Research and Evidence at the charity Crohn's & Colitis UK, said: "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."
"This early research is really exciting because it helps us to 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."
-- BERNAMA-PA MEDIA/dpa
