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The role of intestinal mononuclear phagocytes in driving the chronic inflammation of inflammatory bowel disease

Research group
Active research
Project owner
Institute of Biomedicine

Short description

The inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis are severe, chronic inflammatory disorders of the intestine. IBD results in lifelong suffering for the patients and greatly increases the risk for colorectal cancer. Our research aims to understand the role of specific cell types in driving the inflammation of IBD. To do this, we isolate cells from intestinal tissue of patients with IBD and similar tissue from controls. Using the isolated cells, we study the pathways that are turned on in the IBD patients compared to controls. In this way we can understand the mechanisms underlying the chronic inflammation, which will help develop new treatments.

The inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis are severe, chronic inflammatory disorders of the intestine. These life-long diseases strike young individuals and are chronic health problems worldwide. Moreover, persons with IBD have a greatly increased risk to develop colorectal cancer. Unfortunately, current treatments are insufficient as they have severe side effects and are only effective in some patients. Thus, new treatments are needed to stop the chronic inflammation of IBD that can ultimately lead to colorectal cancer.

The pathogenesis of IBD is not fully understood, but uncontrolled immune reactivity against intestinal microorganisms combined with environmental and genetic factors underlie the disease. Infiltration of proinflammatory immune cells into the intestinal mucosa is induced, which releases cytokines that drive inflammation and lead to tissue damage. As aberrant immune-driven inflammation towards intestinal commensals is central to IBD pathogenesis, our studies focus on understanding how intestinal phagocytic cells, particularly macrophages and dendritic cells, contribute to intestinal inflammation as a means to develop new treatments. To this end, phagocytic cells are isolated from intestinal tissue of IBD patients and non-inflamed controls. Signaling downstream of inflammation-amplifying receptors are studied in phagocyte populations using gene- and protein expression methodologies.  The goal is to define the signaling pathways driving inflammation in patients and whether blocking receptors that initiate the signaling reduces inflammation. In this way we can explored new therapies for IBD. Finding new treatments is critical to relieve the chronic suffering of patients and prevent the development of colitis-associated colorectal cancer. Mechanistic understanding of the molecular mechanisms driving the inflammation gained from this project will reveal new possibilities for treatment strategies for IBD patients.

 

Group members

Charles Caër

Frida Gorreja

Johannes Alfredsson