Out-of-body experiments

A molecule called IL-7 has been linked to intestinal damage in people with celiac disease, according to Calvin Kuo, MD, PhD, the Maureen Lyles D’Ambrogio Professor and professor of medicine. The discovery suggests that blocking IL-7 activity might relieve the condition, said Kuo, who was the senior author of the study. The finding was reported in July 2024 in Nature. Postdoctoral scholar António Santos, PhD, was the lead author.

Celiac disease is an autoimmune disorder in which exposure to gluten — a protein found in wheat, barley and rye — triggers the immune system to attack and destroy the mucosal lining of the small intestine. The only effective treatment is a gluten-free diet for life.

For the study, biopsied intestinal tissue from people with the condition was grown in laboratory dishes. The researchers experimented on the resulting clumps of cells, known as organoids. The study is the first to describe the use of organoids to study autoimmune disease.

“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,” Kuo said, referring to the tissue that lines the inside of the intestines.

The organoids enable new studies of how different cell types interact in people with the disorder. 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.

Prior to this study, there were few ways to directly research celiac disease.

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