Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease, are unpleasant, chronic conditions with few effective treatment options. Now, researchers at KU Leuven and Seoul National University may have found a way to potentially “switch on” the body’s natural tissue repair system.
As the name suggests, IBD is characterized by excessive inflammation in the bowel and gut. While the exact cause is unknown, IBD is an autoimmune disease, where the body’s immune system mistakenly begins to attack the gut lining and other healthy tissues, causing pain, ulcers, bleeding and other gastrointestinal symptoms.
Past studies have attempted to use immunotherapy to adjust the overzealous response, or target bacterial troublemakers to prevent them setting off the immune system in the first place.
But treating the condition is tricky – if the immune response is targeted, inflammation may be reduced but damage to the tissue won’t be repaired either. The roles of immune cells can be quite complex and difficult to unravel.
So for the new study, the researchers focused on one type of immune cell called macrophages, to try to untangle their role in the process. These cells are known to identify and destroy pathogens like bacteria, direct inflammation responses and help repair damaged tissue. Macrophages have been implicated in kicking off IBD in the first place – but they also seem to help repair tissue after a flare-up.
The team investigated the macrophages in the intestines of IBD patients, and found changes in a particular sub-group of macrophages seemed to be linked to different stages of the disease. Some macrophages are sensitive to a messenger molecule called prostaglandin E2 (PGE2), which plays a role in repairing damaged tissue.
"If the patients had acute disease, they had a lower amount of these beneficial cells, and if they went into remission, then amounts of macrophages went up,” says Professor Gianluca Matteoli, lead author of the study. “This suggests that they are part of the reparative process.”
In tests in mice, the team found that animals with ulcerative colitis had fewer PGE2-sensitive macrophages than the healthy control group. When the researchers boosted levels of PGE2, those macrophages responded by releasing substances that improved tissue repair.
To test the inverse, the researchers engineered macrophages to be unable to respond to PGE2 – and sure enough, tissue regeneration slowed. Importantly though, it could be restarted by giving the macrophages liposomes loaded with certain enzymes.
"We already knew that prostaglandins were important for inducing proliferation of tissue cells, but this study shows that they are also important for controlling the inflammatory effect, so moving the body from the acute stage where inflammation dominates to the reparative stage," says Matteoli.
Next, Matteoli and colleague Profesor Seung Hyeok Seok from Seoul National University plan to investigate whether human macrophages work the same way. Ultimately, it could lead to new therapies for treating IBD.
"We want to identify other factors that trip the switch that turns macrophages from inflammatory cells to non-inflammatory cells," says Matteoli. "Then, using the liposome technology that Professor Seok has developed, these could be used to target the macrophages and so produce very precise drugs.”
The research was published in the journal Gut.
Source: KU Leuvin
