12:00 AM
Sep 17, 2009
 |  BC Innovations  |  Targets & Mechanisms

Intercepting IL-15 in celiac disease

A group of American and Japanese researchers has shown that blocking IL-15 signaling decreased inflammation and tissue damage associated with celiac disease in mice.1 They now hope to acquire funding to test the strategy in the clinic, where it could help patients who fail to respond adequately to nutritional therapy.

Each team had separately zeroed in on IL-15 as a key player in lymphoid malignancies and autoimmune diseases. National Cancer Institute researchers are running a Phase I trial of an IL-15 receptor-targeting antibody to treat T cell lymphocytic leukemia,2 whereas the Japanese researchers are studying IL-15's role in gastrointestinal autoimmune disease.3

The two groups have now joined forces to test the IL-15 receptor-targeting antibody in mice that show gut inflammation similar to that seen in patients with celiac disease.

Celiac disease is unique among autoimmune disorders because its triggering antigen has been identified-dietary gluten. Standard care is thus strict avoidance of gluten-containing foods, and the two most advanced therapies in the clinic target gluten in the intestinal lumen before it can interact with the body's immune system to trigger production of proinflammatory cytokines and chemokines (see "The pathogenesis of celiac disease").4,5

The latest findings, published in the Proceedings of the National Academy of Sciences, build on previous work by the Japanese researchers that showed that overexpression of human IL-15 in the mouse intestinal epithelium led to significant inflammation in regions of the small intestine closest to the stomach.3 Those inflammatory lesions showed some of the hallmarks of celiac disease, including significant atrophy of the intestinal villi and infiltration of proinflammatory CD8+ cells.

Based on that finding, the researchers hypothesized that inhibiting IL-15 signaling in the same mice could help reduce inflammation and offer a...

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