New clue in gut inflammation?

New research reveals a surprising twist: how cells meant to protect us may be making things worse in gut diseases like Crohn’s disease and ulcerative colitis.

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 fuelling gut inflammation in conditions like Crohn’s disease and 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 may lead to a new target for future treatments of inflammatory bowel disease.

Caption: Neutrophil DUOX2 drives inflammation in 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, diarrhoea, 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.”

This international collaboration included University of California; the National Institute of Allergy and Infectious Diseases; the Greater Los Angeles Veterans Affairs Healthcare System, U.S.A. as well as academic and clinical colleagues across Ireland.

The research findings are published online in the scientific journal, Proceedings of the National Academy of Sciences (PNAS). 

Journal citation

A.K. Singh, M. Ainciburu, K. Wynne, S.A. Bhat, A. Blanco, I. Tzani, Y. Akiba, S.J. Lalor, J. Kaunitz, B. Bourke, V.P. Kelly, G.A. Doherty, C.S. Zerbe, C. Clarke, S. Hussey, & U.G. Knaus, De novo DUOX2 expression in neutrophil subsets shapes the pathogenesis of intestinal disease, Proc. Natl. Acad. Sci. U.S.A. 122 (19) e2421747122, https://doi.org/10.1073/pnas.2421747122 (2025).