New mouse model for celiac disease to speed res
Celiac disease is an autoimmune disorder that affects an estimated 1% of people worldwide. It causes gastrointestinal symptoms and damage to the lining of the small intestine when someone eats gluten, a protein found in grains such as wheat, barley and rye.
There is no cure, and the only effective treatment is a gluten-free diet, which can be difficult to maintain. Even the most careful celiac patients can accidentally ingest gluten through unknown ingredients in processed food or cross-contamination from foods containing gluten that are prepared nearby or with the same cooking equipment.
Even while maintaining a strict gluten-free diet, 40% of celiac disease patients still show signs of inflammation and villous atrophy, or damage to the villi, the small, finger-like protrusions in the small intestine that help absorb nutrients. Therefore, treatments that can reverse or prevent the disease are greatly needed to improve quality of life for people with celiac.
A complex interplay of contributing factors
Scientists do not know the exact cause of celiac disease, but researchers have identified several genetic, immune system, and environmental components that work together to trigger the disease. People with celiac have one of two genetic variants, HLA-DQ2 and HLA-DQ8, that are part of a group of genes that help the immune system recognize foreign antigens and mount an immune response. However, possessing one these variants is not sufficient to develop the disease alone.
Based on studies in celiac disease patients, Jabri and her colleagues have proposed that signs of tissue distress associated with high levels of an inflammatory protein called IL-15 in the lining of the small intestine were required to cause villous atrophy, the hallmark of the disease.
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.
Jabri said that all of these elements must be present in a research model to truly represent the conditions that cause disease in humans.标签：