March 30, 2025
2 mins read

Study Unveils Key Mechanism Behind Crohn’s Disease

This study marks the first time researchers have demonstrated that gamma delta IELs are critical in balancing pro-inflammatory and regulatory immune responses

A team of scientists has uncovered the role of immune cell dysfunction in the development of Crohn’s disease, a chronic inflammatory bowel disease (IBD). The study, led by Mount Sinai researchers, reveals new insights into how abnormal immune responses may drive the onset and progression of the condition, which affects the gastrointestinal (GI) tract.

Crohn’s disease is known for causing persistent inflammation in the digestive system, leading to symptoms such as abdominal pain, diarrhea, weight loss, anemia, and fatigue. The condition is often debilitating, and its exact causes have remained a topic of extensive research.

The Mount Sinai team focused on a specific type of white blood cell found in the GI tract—gamma delta intraepithelial lymphocytes (gamma delta IELs). These cells are essential in maintaining the integrity of the intestinal barrier, preventing infections, and monitoring immune responses in the gut. Interestingly, patients with active Crohn’s disease often exhibit a significant reduction in the number of these gamma delta IELs.

This study marks the first time researchers have demonstrated that gamma delta IELs are critical in balancing pro-inflammatory and regulatory immune responses. The team’s findings suggest that when these cells become impaired, it could contribute to long-term inflammation, particularly in the lower small intestine, a hallmark of Crohn’s disease.

Until now, previous studies had shown a decrease in gamma delta IELs in patients with active IBD, but it was unclear whether the loss of these cells was a cause or a result of the disease. Dr. Karen Edelblum, an Associate Professor of Pathology at the Icahn School of Medicine at Mount Sinai, emphasized that their research provides clarity on this point. “We’ve shown that gamma delta IELs are reduced well before clinical signs of the disease appear in a mouse model of Crohn’s-like ileitis,” she explained.

The study not only confirms the importance of gamma delta IELs but also establishes a timeline of immune dysfunction leading to IBD. This timeline parallels previous findings in human patients, which could offer valuable clues for early diagnosis and intervention.
Importantly, the loss of gamma delta IELs may serve as an early biomarker, allowing doctors to predict disease relapse or assess a patient’s response to treatment. This could pave the way for more personalized and effective therapeutic strategies.
Looking forward, the research also opens the door for new treatment options. If therapies could be developed to restore or enhance the function of gamma delta IELs, it might be possible to better manage Crohn’s disease, maintain remission in patients, or even prevent the disease from developing in individuals at high risk.

With these groundbreaking insights, researchers are hopeful that future treatments may not only address the symptoms of IBD but also target its underlying immune dysfunction, offering a new era of hope for patients suffering from this chronic and often debilitating condition.

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