Immune Imbalance in the Gut May Trigger Celiac Disease

A new study claims that people who have high levels of Interleukin-15 may be primed to develop celiac disease (CD), a digestive disorder that keeps sufferers from eating foods like cereal, pasta, cookies, and beer.

Researchers at the University of Chicago (IL, USA) integrated insights from immunological studies with results of recent genetic genome-wide association studies into a disease model. The researchers claim that genetic data, among others, suggest that viral infections are implicated and that a natural effector pathway is important in the pathogenesis of CD. However, these data also converge with existing immunological findings that CD is primarily a T cell-mediated immune disorder in which CD4(+) T cells that recognize gluten peptides play a central role, via disregulation of Interleukin-15.

To study the CD pathway hypothesis, the researchers recreated the disease in mice by increasing levels of Interleukin-15 in their intestines. Once this occurred, the mice developed all the early symptoms of CD. Adding retinoic acid to the mix only made the symptoms worse, causing inflammation and tissue damage. When the researchers blocked IL-15, however, the CD mice reverted to normal and were once again able to tolerate gluten. The study was published ahead of print on February 9, 2011, in Nature. The suggested pathway is discussed further in 2011 Annual Review of Immunology.

"We still don't understand why Interleukin-15 is disregulated; if there is a disregulation in the intestinal environment, this alone can explain how you can lose tolerance to some food items,” said lead author Bana Jabri, MD, PhD, of the digestive disease research core center. "It is a first time a pathway has been identified; having mice that develop the disease will allow the team to study potential treatments.”

CD is an autoimmune disorder of the small intestine, caused by a reaction to gliadin--a gluten protein found in wheat--and similar proteins found in the Triticeae crops, which includes other common grains such as barley and rye. However, a comparison of genetic pathways as well as genetic susceptibility loci between CD and other autoimmune and inflammatory disorders reveals that CD bears stronger resemblance to T cell-mediated organ-specific autoimmune than to inflammatory diseases.

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