The Novo Nordisk Foundation has awarded William Winston Agace a grant of DKK 60 million for mapping the mechanisms behind immune tolerance in the gut and how chronic inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease affect these processes.
Millions of people globally have the chronic inflammatory bowel diseases ulcerative colitis and Crohn’s disease. The current treatment options for people with these disabling diseases are limited, but this may change in the future.
Based on a grant of DKK 60 million from the Novo Nordisk Foundation’s ambitious Challenge Programme, William Winston Agace, Professor, Department of Health Technology, Technical University of Denmark, Kongens Lyngby and Department of Experimental Medical Science, Lund University, Sweden, will map how these inflammatory bowel diseases disrupt the interaction between the immune system and the microbial environment in the gut.
The project aims to improve understanding of how the immune cells are regulated to maintain tissue homeostasis and how changes in this homeostasis can lead to the development of inflammatory bowel diseases.
The research will facilitate the development of methods to identify whether specific therapies for inflammatory bowel diseases work and will form the basis for developing new types of treatment.
“We do not know why the immune system becomes dysregulated in chronic inflammatory bowel diseases, but this occurs in a complex interaction between the immune system and the environment in the gut, including the microbial environment. In this research, we will deepen the understanding of the role of specific cells in promoting chronic disease and how signals from the microbial environment maintain immune tolerance and tissue integrity,” explains William Winston Agace.
Immune system in the gut carefully balanced
The immune system in the gut protects us from infections. However, this immune system should not respond aggressively towards everything present in the gut, because the gut bacteria have an important role in keeping people healthy by interacting with the immune system.
Immune cells must therefore monitor everything that happens in the gut, but balance and tolerance are needed so that the immune system is not constantly overworked, leading to the risk of developing a chronic inflammatory condition.
The immune cells are located in tissue comprising stromal cells, and much of William Winston Agace’s research project will focus on these cells.
“Research has indicated that stromal cells are very diverse and that they can produce different immunomodulatory molecules that influence how the immune system responds to the environment. One aim of the research is to identify how the stromal cells maintain the local immune balance in the tissue. Our hypothesis is that changes in how the stromal cells regulate this immune balance ultimately contribute to disease. Improving the understanding of the role of stromal cells can therefore lead to identifying new treatment targets for people with inflammatory bowel diseases,” adds William Winston Agace.
Specific cells control the immune balance in the gut
The primary purpose of the research is the basic scientific mapping of how the stromal cells interact with the immune cells in the gut to maintain the immune balance, what signals are involved and how these cells and signals contribute to the immune-mediated pathology of inflammatory bowel diseases.
The research will also identify biomarkers that can reveal whether specific treatments affect how stromal cells regulate gut homeostasis.
Finally, William Winston Agace and colleagues hope that the stromal cells or the product of how the stromal cells regulate the intestinal immune response may themselves become the target of new treatments for people with chronic inflammatory bowel disease.
William Winston Agace explains that part of the research he and his colleagues will carry out over the next 6 years will involve specialised techniques to isolate specific cells and regions in the gut so that they can be closely examined for the first time.
“A research grant of this size is instrumental in driving research forward and conducting studies on human tissue and mechanistic studies on animals. The grant provides a fantastic opportunity for collaborating across disciplines towards a common goal and bringing together leading international experts in understanding how the immune system and gut bacteria interact. This will enable us to explore the subject in great depth, thereby benefitting people with chronic inflammatory bowel disease,” says William Winston Agace.
About the Challenge Programme
The Novo Nordisk Foundation established the Challenge Programme in 2014. Since then, the Foundation has awarded more than DKK 100 million every year for ambitious research focusing on global challenges.
The Challenge Programme targets research projects based on a thematic approach addressing some of the major societal challenges.
In 2022, six researchers have received grants totalling DKK 337 million through the Challenge Programme. Read about all the grants here.