Study reveals the intestinal epithelium's crucial role in the gluten response of celiac disease

In a new paper published today in the journal Gastroenterology, people with celiac disease must navigate everyday life by avoiding gluten, a protein in wheat, rye and barley which can trigger painful symptoms in the gut, impede the absorption of nutrients and raise the risk of other serious long-term issues.

Celiac disease, an autoimmune disorder affecting around 1% of the population, has roughly doubled in prevalence over the past 25 years, yet no treatment is available.

An interdisciplinary team from McMaster University in Canada, along with researchers from the US, Australia, and Argentina, has spent six years uncovering a crucial piece of the puzzle, the initiation and location of the gluten response.

They found that the inner lining of the upper intestine, called the "epithelium" composed of a variety of cells that are not classically part of the immune system – also plays an active role in directing the inflammatory response to gluten.

Using microscopic biomaterials in the laboratory, the team created a biologically functioning model of the intestinal epithelium which allowed the researchers to isolate the effects of specific molecules in the epithelial cells of people with celiac disease. The model allowed the researchers to generate and observe the reactions under controlled conditions, an option that is simply not available in extremely complex gut environments of living beings.

In conclusion, the breakthrough study elucidated the critical role of the intestinal epithelium in the pathophysiology of celiac disease. By demonstrating how epithelial cells contribute to the immune response against gluten, the research provided new insights into the mechanisms underlying the disease. These findings underscore the importance of targeting the intestinal epithelium in developing novel therapeutic strategies for celiac disease. The study's results mark a significant advancement in our understanding of gluten sensitivity and open avenues for more effective treatments.

References: Rahmani, S., et al. (2024) Gluten-Dependent Activation of CD4+ T Cells by MHC Class II–Expressing Epithelium. Gastroenterology. doi.org/10.1053/j.gastro.2024.07.008.