For years, a powerful inflammatory molecule called interferon-gamma (IFN-γ) has been known as a major cause of gut injury during these treatments. But a new study shows that IFN-γ can also promote healing—as long as it works together with another immune molecule, interleukin-10 (IL-10). “This work reveals a completely new role for inflammatory signaling in tissue repair,” comments Julius Fischer, MD, first author of the study.

The scientists found that a specialized group of immune cells, called regulatory T cells (Tregs), produce both IFN-γ and IL-10 when the intestine is injured. This unique combination sends “repair instructions” to intestinal stem cells. IFN-γ jump-starts the regeneration process, while IL-10 protects the stem cells from being overworked or destroyed. “Now we have seen that under certain conditions the immune system uses inflammatory signals to start healing”, says Sascha Göttert, PhD candidate and co-first author of the study.

Using mouse models and human “mini-intestines” grown in the lab, the team found that IFN-γ on its own can damage intestinal stem cells, while IL-10 alone is insufficient to repair the tissue. However, when combined, the two molecules activate essential growth pathways that work together to rebuild the gut lining. This balanced signaling enables the intestine to recover even after severe injury.

The findings shed new light on how the body naturally repairs treatment-related damage and points toward potential therapies that could boost gut regeneration, reduce complications such as graft-versus-host disease, and help patients tolerate cancer therapy more safely. “By understanding how Treg cells coordinate these signals, we can begin developing strategies to protect the gut during intense cancer treatment”, concludes Hendrik Poeck.

Overall, the study uncovers a surprising cooperation between inflammatory and protective signals that allows the gut to rebuild itself after severe damage. These insights may pave the way for new therapies that strengthen intestinal healing during aggressive cancer treatments.

Read the full article in Signal Transduction and Targeted Therapy:
https://www.nature.com/articles/s41392-025-02476-5

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