Immune cell dysfunction may trigger Crohn's disease development

A research team from Mount Sinai has revealed important information about how immune cells function in the gastrointestinal tract. Their findings, published in Science Immunology, offer insights into Crohn's disease, an inflammatory bowel disease. Crohn's disease can cause serious symptoms like abdominal pain, diarrhea, weight loss, and fatigue. It happens when there is chronic inflammation in the GI tract. Although inflammation is usually a response to infection, if it continues for too long, it can harm healthy cells and tissues. The researchers focused on a type of white blood cell in the GI tract called intraepithelial lymphocytes (IELs). These cells help fight infections and monitor the intestinal barrier. They found that gamma delta IELs are often lower in patients with active Crohn's disease. This study is the first to demonstrate that gamma delta IELs play a vital role in controlling inflammation. The researchers discovered that these cells become impaired during the early stages of Crohn's disease, shortly before visible symptoms appear. This loss of gamma delta IELs can lead to increased inflammation and tissue damage. The team conducted experiments using mice that mimicked Crohn's disease. They found that pro-inflammatory proteins disrupted the communication between gamma delta IELs and other intestinal cells, leading to a significant drop in gamma delta IELs. This change weakens the immune system's ability to control inflammation. The researchers suggest that tracking loss of gamma delta IELs could help predict disease flare-ups or how well patients respond to treatments. They also believe future therapies could be developed to enhance the function of these cells, potentially helping to prevent or manage Crohn's disease. Colleagues from Rutgers University, Case Western Reserve University, and Children's Hospital of Los Angeles contributed to this research.