DUOX2 expression in inflammatory bowel disease patients. (A) mRNA expression of indicated genes in intestinal tissues, whole blood and purified blood neutrophils of healthy controls (HC) and IBD patients (UC, CD). (B) Immunofluorescence images of IBD patient intestinal tissues showing DUOX2 expression in CD66B+ neutrophils. (C) Immunofluorescence image of ulcerative colitis patient intestinal tissues showing colocalization of citrullinated histone H3 and MPO. (D) Immunofluorescence images of CGD-IBD patient tissues with CD66B+MPO+ neutrophils expressing DUOX2. White triangle indicates lamina propria DUOX2+ neutrophils, yellow arrows DUOX2+ epithelial cells. (E) Immunofluorescence images of IBD patient intestinal tissues showing DUOX2 expression (DUOX S12 antibody). Credit: Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2421747122

Scientists have discovered that certain immune cells—called neutrophils—can start making a protein called DUOX2 that they usually do not produce. This surprise activity may be fueling gut inflammation in conditions like Crohn's disease and ulcerative colitis.

The international study led by Professor Ulla Knaus, UCD School of Medicine and UCD Conway Institute shows this unusual protein production might damage the intestine and make these diseases worse. These surprise findings, now published in the Proceedings of the National Academy of Sciences, may lead to a new target for treating inflammatory bowel disease.

Neutrophils are immune cells. They usually help fight infections by attacking bacteria and cleaning up damaged tissues. DUOX2 is a protein that creates chemicals to repel germs but can also damage the body if there is too much of it. Normally, neutrophils do not contain DUOX2 but in people with gut disease, some neutrophils start making this protein (called "de novo" expression).

Dr. Ashish Singh, postdoctoral researcher and first author explained, "Our findings show that the new DUOX2 protein can lead to too many reactive chemicals being produced, which causes inflammation in the gut. This makes the disease worse. The gut can get more irritated, leading to more pain, diarrhea, and long-term problems. If we can stop neutrophils from making DUOX2 or discover inhibitors, it might help clinicians to treat gut inflammation in the future."

Prof. Knaus said, "Interestingly, we have seen early indications in our research that neutrophil DUOX may also be a promising therapeutic target in acute inflammation across other organs as well. This presents a breakthrough for drug discovery in neutrophil-driven inflammatory diseases."

More information: Ashish K. Singh et al, De novo DUOX2 expression in neutrophil subsets shapes the pathogenesis of intestinal disease, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2421747122  Journal information: Proceedings of the National Academy of Sciences