"At the clinic, we mainly see young patients who are just beginning their professional lives," Prof. Hegazy explains. "So far, we have only been able to slow down the progression of the disease and alleviate symptoms. But not all patients respond well to existing treatments, so new therapeutic approaches are urgently needed."
The team’s investigation focused on a signaling molecule known as oncostatin M (OSM). Produced by certain immune cells, OSM is a protein that normally plays a role in tissue repair and cell differentiation. However, in the context of IBD, it appears to malfunction, acting instead as a powerful pro-inflammatory catalyst. The researchers observed that OSM triggers a cascade of other inflammatory factors, creating an excessive immune response that the body cannot easily shut down.
A key finding of the research was the correlation between OSM levels and treatment outcomes. "It was especially interesting for us to see that patients with high levels of oncostatin M do not respond to several common therapies," says Prof. Hegazy. This observation suggests that OSM is not just a driver of the disease but also a critical biomarker. High levels of the protein could serve as an early warning sign for clinicians, predicting that a patient is likely to fail standard treatments and may require a more aggressive or specialized approach from the outset.
To understand the mechanics of this "uncontrolled chain reaction," the research team utilized state-of-the-art single-cell sequencing. This technology allowed them to examine the behavior of individual cells within the inflamed tissue with unprecedented precision. By comparing healthy gut tissue with samples from IBD patients, they discovered that inflamed tissue contains a significantly higher number of cells equipped with receptors for oncostatin M. Furthermore, they found that another messenger substance, Interleukin-22 (IL-22), plays a paradoxical role in this process.
IL-22 is generally considered a protective protein; its primary function is to support the cells lining the gut and maintain the integrity of the intestinal barrier. However, the Charité team discovered that in the presence of chronic inflammation, IL-22 actually increases the number of OSM receptors on the gut lining. This makes the tissue hypersensitive to the inflammatory effects of oncostatin M.
"These two immune messengers work together and amplify the inflammation, drawing more immune cells into the intestine, like a fire that keeps getting more fuel and spreads," Prof. Hegazy notes. This synergy explains why the inflammation in some patients becomes so severe and resistant to traditional intervention. When the team used models to specifically block the binding sites for oncostatin M, they observed a dramatic reduction in both the intensity of the chronic inflammation and the associated risk of developing cancer.
