Gluten reaction trigger identified, could lead to new celiac treatments

Scientists have made a breakthrough that could lead to new treatment options for celiac patients. The team identified how and where the gluten response begins, with certain cells playing a bigger role than thought.

Like other autoimmune disorders, celiac disease occurs when the body mistakenly launches an immune response against a harmless molecule – in this case the trigger is gluten, a protein found in many cereal grains. Consuming these foods leads to a range of unpleasant symptoms, and the only treatment is a strict diet.

To help find a better option, the researchers on the new study investigated how and where the gluten response actually begins. In studies in mice and lab-grown mini-intestines (called organoids), they observed the responses of different cells to the presence of gluten.

“This allowed us to narrow down the specific cause and effect and prove exactly whether and how the reaction takes place,” said Tohid Didar, corresponding author of the study.

It turns out that epithelial cells – those that make up the inner lining of the upper intestine – respond to gluten by actively stimulating the release of CD4+ T cells. In turn, these helper cells trigger an overactive immune response that’s felt as the common celiac symptoms. It was widely thought that the response involves immune cells only, although epithelial cells were suspected to play a role. Now, the team says, that suspicion has been confirmed.

The team also uncovered another factor at play. The epithelial cells send stronger signals to the immune cells in the presence of Pseudomonas aeruginosa, a pathogenic bacteria species that’s not normally a healthy part of the human microbiome.

The researchers say that the discovery could provide new targets for developing drugs that potentially treat or prevent celiac disease. Testing for P. aeruginosa could also help identify patients most at risk of developing the condition.

“The only way we can treat celiac disease today is by fully eliminating gluten from the diet,” said Elena Verdu, corresponding author of the study. “This is difficult to do, and experts agree that a gluten-free diet is insufficient.”

The research was published in the journal Gastroenterology.

Source: McMaster University

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