The Epigenetic Reign of Intestinal Homeostasis and Aberrancies therein in Celiac Disease

In celiac disease the main hallmark of the disease is the defectively differentiated intestinal epithelium which leads to food malabsorption. We have discovered that epigenetic gene-silencer, called polycomb, controls the intestinal homeostasis between intestinal stem cells in crypts and mature epithelium in villi. In response to gluten ingestion, consequent aberrant polycomb activity was found to cause imbalance in intestinal homeostasis (Oittinen et al. 2017 Stem Cells). Lifelong gluten-free diet (GFD) is the only accepted treatment option for patients with celiac disease. In refractory celiac (RCD) patients even rigid adherence to GFD is not remedial and in untreated type II RCD cases prognosis is very poor with 44-58% 5-year survival rate. In this project we seek to study the function of these epigenetically dysregulated genes in celiac disease. We anticipate that the results will reveal novel pathogenic mechanisms and improve the diagnosis of the early celiac disease.