NYC Gazette

A research team led by Mount Sinai has made significant progress in understanding cellular mechanisms that may lead to Crohn's disease. Published in Science Immunology on March 21, the findings highlight abnormal immune cell functions as potential contributors to the development of inflammatory bowel disease (IBD).

Crohn’s disease, a type of IBD, results in chronic inflammation of the gastrointestinal (GI) tract, leading to symptoms like abdominal pain, diarrhea, and fatigue. Inflammation, although the body's natural defense against infection, can cause harm if prolonged. Key in the protective roles are intraepithelial lymphocytes, or gamma delta IELs, in the GI tract, which are notably reduced in patients with active Crohn’s disease.

The study, for the first time, indicated that gamma delta IELs are crucial in maintaining the balance between pro-inflammatory and regulatory immune responses. Their impairment is linked to the onset and progression of long-term inflammation in the lower small intestine.

Karen Edelblum, PhD, the study's corresponding author and an associate professor at the Icahn School of Medicine at Mount Sinai, said, “Previous studies assessing patient biopsies revealed a decrease in gamma delta IELs in those with active IBD. However, it was unknown whether the loss of these cells was a cause or consequence of disease.” She added, “Our findings now show that gamma delta IELs are substantially decreased weeks before clinical or histological evidence of disease in a mouse model of Crohn’s disease-like ileitis."

Using a mouse model, the researchers found that before tissue damage, pro-inflammatory proteins disrupted the communication between gamma delta IELs and nearby intestinal cells, resulting in their substantial losses and compromised barrier surveillance. They also identified that gamma delta IELs lost their suppression ability, possibly contributing to early inflammation activation in Crohn’s disease.

The reduction of gamma delta IELs could potentially serve as a predictive biomarker for disease relapse or treatment response. Future therapies aimed at enhancing the function of these cells could help prevent disease development or maintain remission in IBD patients.

The study was conducted with contributions from Rutgers University, Case Western Reserve University, and Children’s Hospital of Los Angeles and supported by grants from various health organizations, including the National Institutes of Health.