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Blocking interleukin 15 may help restore oral tolerance to gluten

August 20, 2017

They knew that many patients with this disease had high levels of Interleukin 15 in their intestines. When the researchers increased the levels of this signaling molecule in mouse intestine, the mice developed all the early symptoms of celiac disease. Adding retinoic acid to the mix only made the symptoms worse.

When they blocked IL-15, however, the diseased mice reverted to normal, and were once again able to tolerate gluten.

Clinical trials of medications that block IL-15 are already underway for patients with rheumatoid arthritis, another inflammatory disorder. Early results, have been encouraging. Blocking IL-15 or IL-15 signaling may be a way to restore oral tolerance to gluten and allow effective responses to vaccines aiming at preventing development of celiac disease, Jabri said.

This study is the first to identify an abnormal pathway leading to loss of tolerance to dietary antigens. It suggests that a "dysregulated intestinal environment may be the underlying cause for food allergies," Jabri said. What type of dyregulation is responsible for food allergies, such as to peanuts, is not yet known.

Although the IL-15 plus retinoic acid combination leads to inflammation and tissue damage in those at risk for celiac disease, the authors suggest that for those who, for genetic reasons, are less susceptible, the same combination could help enhance vaccines against several bacterial infections that cause diarrheal diseases. Children in developing countries often lack vitamin A. But by vaccinating them with selected bacterial proteins plus vitamin A, instead of using live viruses, they may be able to reduce the risks and increase the protective response.

SOURCE University of Chicago