study discovers origin of gluten response

The upper intestine epithelium (inner lining) plays a crucial role in activating the immune system in coeliac disease, according to new research.

Coeliac disease is a chronic autoimmune disorder that affects about 1% of people. Its symptoms, which vary considerably, are triggered by exposure to gluten – proteins found in certain cereal grains like wheat, rye, and barley.

“The only way we can treat coeliac disease today is by fully eliminating gluten from the diet,” says Elena Verdu, professor of gastroenterology at McMaster University in Canada and co-author of the new paper.

“This is difficult to do, and experts agree that a gluten-free diet is insufficient.”

It had previously been thought that the inflammatory response to gluten occurred inside the gut wall and exclusively involved immune cells.

Verdu and colleagues created an organoid model of the intestinal epithelium which allowed them to determine that epithelial cells play an important role by alerting immune cells to the presence of gluten in coeliac disease.

Verdu says this could stimulate research into drug delivery to inhibit this newly found role of the epithelium, using drugs already in clinical trials.

They also found that the epithelium sends stronger signals to immune cells when pathogens are also present.

This means that it may be possible to detect the pathogen and inhibit the interactions between gluten and the gut epithelium, to prevent an at-risk person from developing coeliac disease.

The paper, “Gluten dependent activation of CD4+ T cells by MHC class II-expressing epithelium”, is published in the journal Gastroenterology.