Simon Koplev, assistant professor of computational biology at KTH. Photo: Jon Lindhe, KTH

Published Sep 11, 2026

Researchers from KTH, Oxford and Cambridge have discovered how connective tissue cells can change and be reprogrammed in Crohn’s disease. This breakthrough could lead to new treatments for the chronic bowel disease.

Crohn’s disease is an acute, lifelong inflammatory condition of the digestive tract which causes symptoms such as abdominal pain, diarrhoea, fatigue and weight loss. The condition can vary in severity over time and affects approximately 3.2 people in every 1,000. 

“The disease severely impacts quality of life and has no known cure. Better understanding of how immune cells and fibroblasts are dysregulated is essential to develop an effective therapy,” says Simon Koplev , assistant professor of computational biology at KTH.  

Koplev and his colleagues at SciLifeLab examined individual cells in the intestinal wall using a range of groundbreaking methods in single-cell and spatial transcriptomics, a technique developed at KTH. The method makes it possible to see which genes are active in a tissue and exactly where that activity is taking place. 

"The resolution of these techniques has improved in recent years such that individual cells can be clearly distinguished,” Koplev says. “These innovations, as we show in the paper, can reveal neighbourhoods of cells such as immune aggregates, inflamed ulcers, and fibrotic regions, offering unprecedented insight into human disease such as Crohn’s disease." 

Novel therapeutic strategies

The research team discovered that inflammation and fibrosis occur in two separate tissue environments, each populated by different types of stromal cells – the connective tissue cells of an organ. They found repeated inflammation can permanently "reprogram" fibroblasts into a harmful state that continues to attract immune cells even after inflammatory signals disappear.  

The findings were published in Nature Immunology. 

"In the paper, we show how anatomical structures of the intestinal wall have distinct connective tissue formed by fibroblast cell types. During Crohn’s disease, some such fibroblasts remember recent immune activation for up to three weeks,” Koplev says. 

The next step is to identify novel therapeutic strategies such as reversing the identified disease-associated fibroblast states. The research team propose to use the molecular insights into fibroblast activation and the corresponding cell line models to screen for drug candidates. 

“Ultimately, if successful, this could complement existing systemic therapies that suppress immune activation, directly targeting pathological niches and fibroblasts in affected intestinal tissues," Koplev says.  

Jon Lindhe