A groundbreaking study has identified a crucial pathway in the gut that could explain why some people develop chronic intestinal inflammation and even cancer. The research, published in Nature Immunology, reveals how two molecules—interleukin-22 (IL-22) and oncostatin M (OSM)—work together to drive harmful inflammation in the intestines, opening new doors for future treatments of inflammatory bowel disease (IBD) and related cancers.
How the Gut’s Defense System Can Turn Against Us
Our intestines are constantly exposed to bacteria and other microbes. To protect us, the gut lining uses a network of immune signals called cytokines. These signals can help repair damage and keep harmful germs at bay. But when this system goes awry, it can trigger chronic diseases like IBD, which includes ulcerative colitis and Crohn’s disease.
IL-22 is one such cytokine. Normally, it helps repair the gut lining after injury. But scientists have long been puzzled by its double-edged nature: in some cases, IL-22 seems to make inflammation and cancer worse, not better. The new study sheds light on why this happens.
The Discovery: IL-22 and OSM Form a Harmful Partnership
Researchers found that IL-22 directly increases the number of receptors for OSM on the cells lining the intestine. This makes these cells much more sensitive to OSM, another cytokine known to be involved in inflammation. When both IL-22 and OSM are present, they work together to keep the gut in a constant state of alarm, attracting more immune cells and fueling ongoing inflammation.
This vicious cycle not only worsens conditions like IBD but can also lead to the development of tumors in the gut—a process known as colitis-associated cancer (CAC).
Proof in Mice and People
To test their findings, scientists used mouse models of chronic gut inflammation. They observed that blocking the OSM receptor in the gut lining protected mice from both inflammation and cancer. Additionally, when they used drugs to block OSM, they saw a reduction in established cancer in the gut.
Importantly, the team also looked at tissue samples from people with IBD. They found that both OSM and its receptor were much higher in inflamed gut tissue compared to healthy tissue. The pattern was remarkably similar to what they saw in their mouse studies, suggesting the same process is at work in humans.
Why This Matters: A New Target for Treatment
Current treatments for IBD don’t work for everyone, and some patients continue to suffer from severe symptoms and a higher risk of cancer. This new research highlights the IL-22–OSM axis as a promising new target for therapy. By disrupting this harmful partnership, it may be possible to reduce inflammation and lower cancer risk in people with chronic gut diseases.
What’s Next?
The study’s authors believe that drugs targeting OSM or its receptor could offer hope for patients who don’t respond to current treatments. Further research and clinical trials will be needed to turn these findings into new therapies.
“Our findings reveal a previously unknown mechanism by which OSM supports intestinal pathology and highlight the IL-22–OSM axis as a promising therapeutic target for inflammatory bowel disease and CAC,” the researchers conclude.
This discovery could mark a turning point in the fight against chronic gut diseases, offering new hope for millions affected worldwide.
