Immune cell-mesenchymal cell crosstalk in the chronic inflammation of inflammatory bowel disease
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 and greatly increases the risk to develop colorectal cancer and intestinal strictures, which obstruct food movement in the intestine. We aim to understand the role of specific cell types and protein mediators in driving the inflammation and stricture formation. We isolate cells from intestinal tissue of IBD patients and controls. Using these cells, we study the signaling pathways and protein mediators that are increased in IBD patients compared to controls using transcriptional analysis and proteomics approaches, respectively. By understanding the mechanisms underlying the chronic inflammation we can develop new treatments for IBD and associated pathologies.
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 and other complications such as intestinal strictures. 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 lead to colorectal cancer and other complications such as strictures.
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 inflammatory immune cells into the intestinal mucosa is induced, which releases protein mediators (cytokines) that drive inflammation and lead to tissue damage. Immune cells, particularly recruited macrophages and lymphocytes, are key drivers of the inflammation. Moreover, the function of these immune cells in an inflammatory environment is tightly linked to mesenchymal cells. That is, in the inflammatory setting, immune cell-mesenchymal cell crosstalk leads to aberrant cell function that perpetuates chronic inflammation and can cause additional pathologies in patients.
Our goal is to understand how intestinal immune cells and mesenchymal cells contribute to intestinal inflammation and stricture formation as a means to develop new treatments. To this end, cells are isolated from intestinal tissue of IBD patients and non-inflamed controls. Signaling pathways induced in cells from inflamed versus control tissue are studied using gene expression technologies. In addition, protein expression is examined using proteomics analysis as well as immunofluorescence microscopy and flow cytometry approaches. The overall goal is to define the signaling pathways and proteins that drive inflammation and stricture formation in patients. In this way we can explore new treatments for IBD, which is critical to relieve the chronic suffering of patients and complications including strictures and colorectal cancer.
Mary Jo Wick
Principal Investigator
Affiliation:
Department of Microbiology and Immunology,
Institute of Biomedicine
Group members
Johannes Alfredsson, PhD student