Organoids mimicking celiac disease show new link between gluten, intestinal damage


 Small, laboratory-grown balls of cells made from the intestinal tissue of people with celiac disease have revealed a previously unknown molecular link between gluten exposure and intestinal damage, according to a study from researchers at Stanford Medicine.

The molecule, called IL-7, has been implicated in other autoimmune diseases including rheumatoid arthritis and multiple sclerosis, but it has never been linked to celiac disease.

The study is the first to describe the use of clumps of cells maintained in a laboratory dish, called organoids, to study autoimmune disease. Unlike previous attempts to model celiac disease in the laboratory, the intestinal organoids grown by the researchers include multiple cell types, including immune cells and the cells that make up the lining of the gut.

The organoids open the door to understanding how different cell types interact in people with the disorder, characterized by an acute sensitivity to gluten, in ways that haven’t previously been possible. For example, the researchers found that levels of IL-7 were elevated in tissue from people with active celiac disease and that blocking its activity eliminated the immune reaction to gluten that damages the intestinal lining.

“These organoids provide an accurate reproduction of what happens in people with celiac disease,” said Calvin Kuo, MD, PhD, professor of medicine and holder of the Maureen Lyles D’Ambrogio Professorship. “If we add gluten to organoids made from intestinal biopsies of people with celiac disease, we see immune activation and killing of the epithelial tissue just like what occurs in patients. But now we can probe what’s happening in a dish — learning about the disease, developing new drugs and maybe even predicting what drugs will work best for individuals. This has not been possible before.”

After obtaining informed consent, Fernandez-Becker collected and shared intestinal tissue biopsies from 81 people with celiac disease and 54 people without celiac disease. Of the 81 people with celiac disease, 59 were actively experiencing symptoms while the remaining 22 had successfully reached remission after sticking to a gluten-free diet.

Santos then exposed organoids made from the biopsied tissue to a component of gluten known to trigger the disorder. Those made from intestinal tissue from people with celiac disease responded dramatically. Epithelial cells that make up the lining of the gut ramped up their production of a molecule called IL-15 associated with the disorder, the number of immune cells called CD4 T cells that specifically recognize gluten began to increase and other immune cells called B-cells churned out antibodies to a protein called type 2 transglutaminase, or TG2.

TG2 does not normally induce an immune response, and the presence of these autoantibodies is a key hallmark of celiac disease often used to diagnose the disorder. Finally, immune cells called CD8 T cells began to attack and kill the epithelial cells — likely at the behest of their CD4 counterparts.


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#CeliacDisease #Organoids #GlutenSensitivity #IntestinalHealth #GutResearch #MedicalBreakthrough #DiseaseModeling #GlutenFree #IntestinalDamage #Biotech #MedicalResearch #GutHealth #Microbiome #AutoimmuneDisease #HealthScience

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