Mount Sinai research explores Crohn's disease immune mechanisms

A research team from Mount Sinai has made a significant discovery regarding Crohn's disease. Their findings were published in Science Immunology on March 21. They identified mechanisms involving abnormal immune cell function that may lead to this inflammatory bowel disease. Crohn's disease causes chronic inflammation in the gastrointestinal (GI) tract. Common symptoms include abdominal pain, diarrhea, weight loss, anemia, and fatigue. While inflammation is a normal response to infection or injury, long-term inflammation can harm healthy cells and tissues. The study highlighted the role of a type of white blood cell called intraepithelial lymphocytes, or gamma delta IELs. These cells are crucial for protecting the intestinal barrier and preventing infections. Researchers found that these gamma delta IELs are often reduced in patients with active Crohn's disease. This research is the first to show that gamma delta IELs help regulate immune responses and that they are impaired when Crohn's disease worsens. Previous analyses of patient tissue samples showed fewer gamma delta IELs in those with active inflammatory bowel disease (IBD). However, it was unclear if their loss caused the disease or was a result of it. Using a mouse model, researchers discovered that gamma delta IELs decreased weeks before any clinical signs of disease appeared. They observed that inflammatory proteins disrupted communication between gamma delta IELs and nearby intestinal cells, leading to the death of many of these protective cells. This loss of gamma delta IELs may play a role in the activation of inflammation seen in Crohn's disease. Researchers suggest that monitoring these cells could help predict disease relapses or a patient's response to treatment. They also believe that therapies enhancing the function of gamma delta IELs may help maintain remission in IBD patients or prevent the disease in those at risk. The study included contributions from researchers at Rutgers, Case Western Reserve University, and Children’s Hospital of Los Angeles. Financial support came from the National Institutes of Health and other organizations.