Celiac disease is an autoimmune disorder that affects approximately 1% of the population and whose prevalence has doubled in the last 25 years. However, there is no treatment and those affected must avoid the consumption of gluten, a protein found in wheat, rye and barley that can cause painful symptoms in the intestine, prevent the absorption of nutrients, and increase the risk of developing other serious health problems in the long term.
An interdisciplinary team of medical and engineering researchers based at McMaster University in Canada that also included colleagues from the U.S., Australia and Argentina has spent the past six years working to decipher a critical piece of the puzzle in the search for a cure: how and where the response to gluten begins.
It had previously been thought that the inflammatory response to gluten occurred within the intestinal wall and involved immune cells exclusively, but in an article published in the journal GastroenterologyThe team has shown that there is more to it, as they have discovered 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.
How the immune system is activated in celiac disease
Using microscopic biomaterials in the lab, the team created a biologically functional model of the intestinal epithelium that allowed researchers to isolate the effects of specific molecules on the epithelial cells of people with celiac disease. The model allowed researchers to generate and observe the reactions under controlled conditions, an option that is simply not available in the extremely complex intestinal environments of living beings.
They were able to observe how molecules alert immune cells to the presence of gluten and definitively conclude that the epithelium plays a key role in activating the immune system in celiac disease. Such a mechanism had been postulated before, but never proven. The answer to this controversial question is expected to advance the development of new drugs.
Pinpointing the origin of the immune response could spur research into drug delivery to inhibit this newly discovered function of the epithelium in celiac disease.
“The only way to treat celiac disease today is to completely eliminate gluten from the diet. This is difficult to do, and experts agree that a gluten-free diet is insufficient,” said Elena Verdu, corresponding author of the paper, professor of gastroenterology and director of McMaster’s Farncombe Family Digestive Health Research Institute.
Pinpointing the origin of the immune response could spur research into delivering drugs to inhibit this newly discovered function of the epithelium, using drugs already in clinical trials, Verdu says. “This allowed us to narrow down the specific cause and effect and show exactly if and how the reaction occurs,” says Tohid Didar, corresponding author of the paper and associate professor in McMaster’s School of Biomedical Engineering who holds the Canada Research Chair in Nanobiomaterials.
Another significant finding of the study is that after detecting gluten, the epithelium sends stronger signals to immune cells if pathogens are also present. This means that in the future it may be possible to detect the pathogen in a person at risk of developing the disease and inhibit interactions with gluten and the intestinal epithelium to prevent the disease, concludes the paper’s lead author, Sara Rahmani, a PhD candidate in the Verdu and Didar labs.
