Cell Signaling Influence Inflammatory Bowel Disease

Understanding cellular mechanism can improve treatment of chronic inflammatory disease.

Findings published in Nature Communications provided insight into chronic inflammatory disease, and how individual cells in the body can understand different signals.

Prior research has shown that when the body’s natural immune system is disturbed and the response runs out of control, chronic inflammatory disease begins to develop. In order to tune the immune response, it is reliant on the concentrated action of different immune cells, which communicate through complex networks of the signaling molecules, cytokines.

“Our immune systems are highly sophisticated and mechanisms of communication between different cells must be exquisitely controlled,” said researcher Dean Jackson. “In inflammatory diseases such as IBD, this fine tuning is lost and the system runs out of control — like a snowball running down a hill. If we can develop better drugs to manipulate cell communication the outcome for patients should be improved.”

Certain cytokines either enhance or suppress inflammation, and their balance plays a role in determining the severity of the response. When cytokine stimulation is imbalanced, it can lead to the activation of immune cells that turn against the body, and causes tissue damage.

“There are dozens of cytokine molecules, and we have a good understanding of what they do in our bodies,” said study leader Pawel Paszek. “However, how individual cells in our bodies can make sense of different signals eluded us. We were excited when we hit upon this understanding.”

The results of the study showed that cells have a highly variable ability to react to cytokine simulation, and that it is dramatically influenced by other cytokines in their environment.

“Cells are constantly bombarded by different messages,” said researcher Antony Adamson. “In our experiments we showed that different combinations of these cytokine messages resulted in drastically behavior. Essentially the cells are trying to gather and understand all the information around them, but rather than listening to multiple news bulletins playing at once, they can switch between different channels.”

Out-of-control cytokine signaling is associated with several inflammatory conditions, such as ulcerative colitis and Crohn’s disease. Clinically, a major drug for managing inflammatory bowel disease (IBD) targets is a cytokine called tumor necrosis factor alpha (TNF), and its actions were also investigated in the study.

“TNF is a very important molecule and our team has shone light on the way cells control excessive amounts of the TNF, which may be important for the progression of chronic inflammatory diseases,” said researcher Mike White.

The findings will help provide potential options for IBD patients in the future.

“Though some years away, ‘systems medicine’ could save the NHS money, and protect patients from the trauma of trying medicines for months or even years which fail to impact on the distressing symptoms of IBD,” said Professor Werner Muller, scientific coordinator of SysmedIBD. “This research by Dr Paszek is another step along the path of making this approach a reality.”