HMN 2025: how cells in small intestine of patients with celiac disease communicate with one another

A new comprehensive atlas of cells fills gaps in knowledge on how different cells in the intestine act together to drive celiac disease, potentially opening new avenues for future therapeutic intervention.

Celiac disease is a long-term autoimmune condition that affects about 0.5% to 1% of people. A new published collaborative report from scientists at Children’s Health Ireland (CHI), Johnson & Johnson and Trinity College Dublin, created the most detailed map to date of how individual cells behave in the small intestine of people with celiac disease, using a technique called single-cell RNA sequencing. They looked at over 200,000 individual cells from tissue samples of both people with active celiac disease and healthy individuals (all anonymized).

The report was recently published in the journal Cell Reports.

The results showed major differences in the types and activities of cells in the gut lining (epithelium) and the supporting tissue underneath (called the stroma) between people with celiac disease and those without.

The team created an atlas of cells present in the small intestines of both patient types, allowing them to:

• Characterize how these cells are different in disease through identifying which genes are “switched on.”
• Find that genes which are “switched on” in diseased tissues (but not in normal tissues) activate pathways which potentially drive the disease.
• Identify pathways through which different cells can communicate with each other to drive the tissue damage, which is characteristic of celiac disease.

The team found that in people with celiac disease:

• There were more stem cells and secretory cells, but fewer cells that absorb nutrients, which matches known damage like villus atrophy (flattening of the gut lining) and crypt hyperplasia (overgrowth of certain gut structures).
• The supporting stromal cells also changed, especially a type of cell called fibroblasts, which became more active and more common.

The study found that immune signals, especially from two immune system proteins (IL-1? and IFN-?), may be encouraging these fibroblasts to support changes in the gut lining. This suggests that communication between immune, stromal, and epithelial cells plays a key role in how the gut reacts to gluten in celiac disease.

Overall, this research gives new insight into how different types of cells in the gut work together—and change—in response to gluten exposure in celiac disease. The findings allow the team and other researchers to move a step closer towards providing effective therapies for celiac disease.

Patrick Walsh, Clinical Medicine, School of Medicine, Trinity College Dublin, said, “CHI patients’ involvement has been the pivotal factor in this research, which has allowed us to advance knowledge of how this disease occurs and ultimately assist in efforts to open avenues for the development of new treatment approaches. These findings provide a detailed and comprehensive map of the cellular landscape in the inflamed intestine of young celiac patients and has the potential to inform future directions for researchers working internationally to tackle this disease.”

Seamus Hussey, Consultant in Gastroenterology, Hepatology, Intestinal Failure and Transplant Medicine in CHI at Crumlin, said, “Every year, 150–200 children in Ireland are newly diagnosed with celiac disease, a condition that currently requires a lifelong gluten-free diet. This groundbreaking research stems from existing strong partnerships between researchers in Trinity and Children’s Health Ireland at Crumlin. Illuminating new intricate immune pathways and connections in pediatric celiac disease marks a pivotal step toward developing novel, immune-based medical treatment options for patients worldwide.”

Darren Ruane, Director of translational science and medicine, immunology, Johnson & Johnson, said, “This exciting collaboration between Johnson & Johnson, Immunology and the research teams at Trinity and CHI, has provided significant impact to the celiac disease field. These efforts have identified novel pathways related to celiac disease pathogenesis and highlighted the previous unknown role of stromal-immune cellular communication in disease. This research will enable new therapeutic target identification.”