HMN 2025: How Gut cells aid intestinal healing, hope for IBD patients

A team led by scientists at King’s College London, in collaboration with national and international partners, has discovered how a specific group of immune cells in the gut—Group 3 Innate Lymphoid Cells (ILC3s)—promote intestinal health by activating a powerful signaling molecule called Transforming Growth Factor Beta 1 (TGF-?1). The findings could lead to new treatments for inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis.

Published in Mucosal Immunology, the study shows that ILC3s not only produce TGF-?1 but also activate its latent form through mechanical and enzymatic processes. This activation triggers two critical effects:

• Calming inflammation: TGF-?1 helps create “peacekeeper” immune cells called regulatory T cells, which stop the immune system from attacking the gut.
• Repairing tissue: It also triggers a repair program in the cells that form the gut lining, helping wounds heal, and the barrier stay strong.

Importantly, these mechanisms were observed in both mouse and human models, highlighting their relevance for human health. The researchers also found that, even in inflamed tissue from patients with Crohn’s disease and ulcerative colitis, ILC3s retain the machinery to activate TGF-?1—suggesting this pathway remains functional during disease.

Why it matters: IBD affects millions worldwide, and current treatments often focus on reducing inflammation rather than repairing the gut lining. This discovery suggests a new approach—supporting the body’s own healing process.

Dr. Joana F Neves, senior author from King’s College London, said, “Our findings identify ILC3s as central players in gut homeostasis. By harnessing their ability to activate TGF-?1, we could develop new strategies to promote healing and restore balance in patients with IBD.”

Dr. Diana Coman, first author from King’s College London, said, “It was exciting to reveal how ILC3s work behind the scenes—activating TGF-?1 through mechanical and enzymatic processes to protect and repair the intestine. It’s a fascinating mechanism with real therapeutic potential.”

The study underscores the potential of therapies aimed at boosting ILC3s function or preventing their depletion, which is commonly seen in IBD. Future approaches might include expanding ILC3s populations or using organoid-based systems to generate autologous ILC3s for transplantation—a strategy that is currently being developed by the Neves research team.

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