Researchers from the Centre d'Immunologie de Marseille-Luminy (CIML), led by Dr. Achille Broggi, have uncovered a key mechanism that slows tissue repair in the intestines during inflammation. This discovery, published in the prestigious journal Cell, could revolutionize the treatment of chronic inflammatory bowel diseases (IBD), which affect more than 250,000 people in France. Until now, most treatments have focused on reducing inflammation. Although biologic therapies and anti-inflammatory drugs have greatly improved symptoms in IBD patients, only 50% of them achieve complete remission. The remaining patients often suffer from incomplete healing of the intestinal lining and frequent relapses. This new discovery offers hope for designing therapies that can help these patients repair their intestines more effectively and achieve complete remission.
The team led by Dr. Broggi, in collaboration with co-senior author Dr. Ivan Zanoni from Boston Children’s Hospital and Harvard Medical School, has identified that a protein called interferon lambda (IFN-λ) plays a crucial role in delaying gut healing. Normally, IFN-λ helps fight viruses by preventing them from replicating, but in people with IBD, this protein is produced in abnormal amounts during inflammation. In the chronically inflamed intestines of these patients, IFN-λ can block the repair process, consequently delaying remission.
Using advanced experimental models, such as intestinal organoids (tiny "mini-guts" grown from patient cells in a dish), the research team was able to trace the molecular pathway activated by IFN-λ. "We discovered that interferon lambda is abnormally high in IBD patients, which leads to the increased production of another protein, ZBP1, in intestinal cells. ZBP1 acts as a sensor of cellular stress and activates a cascade that destroys intestinal stem cells, preventing them from regenerating the epithelial layer," explains Dr. Broggi.
This breakthrough opens the door to new therapeutic approaches. "Our discovery could have major implications not only for IBD patients but also for people undergoing radiotherapy, where intestinal damage is a common side effect," says Dr. Julien Mambu of CIML, the first author of the paper. "By specifically targeting this mechanism, we may be able to accelerate gut healing in these patients."
The next phase of research will focus on working with clinicians and pharmaceutical companies to develop treatments that target this molecular pathway, with the goal of significantly improving the quality of life for IBD patients.
Nouvelles perspectives thérapeutiques pour les Maladies Inflammatoires Chroniques de l’Intestin | CNRS Biologie
