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Certain environmental factors may come into play as well. In 2017, for example, Jabri and her team discovered that a common and relatively harmless virus can cause changes to the immune system that set the stage for celiac. All of these factors work together to trigger an autoimmune response when someone ingests gluten that causes villous atrophy. All the puzzle pieces fall into place
For more than 20 years, researchers have attempted to develop a mouse model for celiac that reflects these conditions. However, none of these models resulted in mice with one of the HLA gene variants that also developed villous atrophy in response to gluten.
In celiac, the main feature of disease is tissue destruction of the small intestinal lining. This new HLA-DQ8 mouse model is unique because it's the only one that actually develops villous atrophy when the animal does eat gluten. In addition, once the mice are placed on a gluten-free diet, their small intestine can recover and heal, just as in humans with celiac disease." Valerie Abadie, PhD, research assistant professor at UChicago and lead author of the study
Jabri said that all of these elements must be present in a research model to truly represent the conditions that cause disease in humans.
"It's like a puzzle where different pieces need to come together for everything to fall into place," Jabri said. "If you have a model where only one piece of the puzzle causes the disease because it's in a laboratory setting, then you cannot test how to block or interfere with the other components. You need to have a setup where you have the entire complex interplay that takes place for the development of celiac disease."
The new mouse model provides a vital tool for developing new treatments to reverse celiac once it has developed, or prevent it from developing in people at risk for the disease. Researchers will be able to identify new targets for drugs and then test them in a model that faithfully represents the condition in humans.
"This wouldn't be possible without first conducting human studies to understand the nature of the disease," Jabri said. "Now, using the mouse model, we can interrogate more and apply what we learned back into the human system. The integration of those two approaches is very important." Source: Journal reference:
Abadie, V., et al. (2020) IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease. Nature . doi.org/10.1038/s41586-020-2003-8 .
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