When inflamed areas of the intestine form scar tissue, the space within the intestinal lumen becomes smaller and more restricted, causing symptoms of intestinal obstruction. Currently, there are no drug treatments available for this complication. As fibrosis worsens, surgery eventually becomes the only option.
Researchers have found that the greatest accumulation of scar tissue occurs in the submucosa (the layer of tissue beneath the lining of the intestine). This indicates that the submucosa may be the starting point where scarring begins.
The inflammation that characterizes Crohn’s disease causes clusters or aggregates of immune cells to form in the submucosa. Using single-cell RNA sequencing (scRNA-seq) to study fibrosis in Crohn’s disease, researchers found that endothelial cells (the cells that normally line blood vessels) cluster abnormally around these immune cell populations (known as Crohn’s disease lymphocyte aggregates, or CLA). These clusters of vascular cells signal scar-forming cells (fibroblasts/myofibroblasts) either directly or through macrophages to begin producing excess collagen or scar tissue. This suggests that these Crohn’s disease lymphocyte aggregates may play an important role in the progression of fibrosis.
Pathologists, gastroenterologists, biomedical scientists and computer experts from the University of Edinburgh and Heriot-Watt University in Edinburgh have worked together for more than six years with researchers from the Earlham Institute and the Sanger Institute to study the cellular and molecular mechanisms of the fibrotic process in Crohn’s disease, in an attempt to identify new therapeutic targets that can be used to treat patients to slow or reverse fibrosis. I am a Crohn’s disease patient. ”
Professor Mark Ahrens, Professor of Pathology and Head of the Edinburgh School of Pathology, University of Edinburgh
This study demonstrates the value of single-cell transcriptomics to complement histological analysis of clinical samples. By linking tissue pathology to cells and signaling mechanisms, disease-associated cell subpopulations that are typically difficult to separate morphologically can be resolved in greater detail.
This paper comes from an international consortium of researchers collaborating to create the Enterocyte Atlas, a research tool to identify and characterize intestinal cells, enabling deeper insight and faster solutions to diseases affecting the digestive system.
At the Earlham Institute, Papatheodorou Group scientists combine computational expertise in single-cell genomics with cutting-edge data science and AI to develop the tools and methodologies needed to integrate data, standardize metadata, build cell atlases, and analyze these atlases across different species.
“Fibrostenosis remains an important and unresolved cause of morbidity in Crohn’s disease, and this study is an important addition to understanding its progression,” said Dr. Gregory Wickham, a postdoctoral fellow in the Papatheodorou Group and co-lead author at the Earlham Institute. “With this collaboration, we were able to combine detailed pathological analysis with single-cell RNA sequencing to characterize how lymphocyte aggregates accumulate during fibrosis and reveal how cells accumulate.” Adjust their actions to drive this process.
“These insights will support continued research in Crohn’s disease aimed at identifying new treatment candidates to better manage fibrostenotic complications.”
Professor Irene Papatheodore, Director of Data Science at the Earlham Institute, said: “The power of single-cell transcriptomics combined with computational analysis lies in its ability to reveal cellular interactions that cannot be identified otherwise. By integrating with clinical pathology, we were able to map the specific cellular neighborhoods within the submucosa where inflammation transforms into permanent scarring. This study will track the progression trajectory of Crohn’s disease and, in the future, identify new targets for interfering with the molecular mechanisms of fibrosis.”
Further analyzes are required to confirm these interactions, so next steps in this study will include increasing the number of intestinal samples analyzed using the same methodology.
This research, funded by the Leona M. Helmsley Helmsley Charitable Trust, the largest private charity focused on Crohn’s disease, is critical to discovering new therapeutic targets to find better treatments for the hundreds of thousands of Crohn’s disease patients who suffer from this painful complication that severely impacts their quality of life.
Co-first author Dr Michael Glinka, a postdoctoral research fellow at the University of Edinburgh’s Institute of Genetic Cancer Research, said: “The fundamental need to understand the drivers of late fibrostenotic lesions in Crohn’s disease led to this collaboration and research between the University of Edinburgh, Heriot-Watt University, the Sanger Institute and the Earlham Institute.”
“Without proper characterization and understanding, we cannot develop new approaches and treatments, so we hope that this study and follow-up studies will help us develop better treatments in the future.”
The paper “Clonal lymphocyte aggregates with endothelial clusters colocalize with submucosal fibrosis in fibrostenotic Crohn’s disease” was published in The Journal of Pathology.
sauce:
Reference magazines:
Glinka, M.et al. (2026). In fibrostenotic Crohn’s disease, Crohn’s disease lymphoid aggregates with endothelial clusters colocalize with submucosal fibrosis. pathology journal. DOI: 10.1002/path.70019. https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.70019
