A novel method which prompts immune cells to aid the repair of damaged intestinal tissues has been developed by researchers at KU Leuven and Seoul National University.
This new approach promises new treatments for inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease. Normally, the immune system defends against pathogens that enter the body. In conditions like IBD, the immune system instead attacks tissues that line the gut, creating ulcers. Some 3.9 million women and 3.0 million women suffer from IBD worldwide.
The origin of IBD is not known, so treatments typically dampen immune response, but at the same time this also obstructs the normal repair of damaged intestinal tissue by other parts of the immune system. Macrophages, for example, consume foreign bodies, clean out debris and direct other steps in inflammatory or repair response through released substances.
Lead author Professor Gianluca Matteoli, an immunologist at the Translational Research Center for Gastrointestinal Disorders (TARGID) KU Leuven, explained the motivation behind the research. “Our idea is that the migration of macrophages to the damaged tissue in IBD is essential to stimulate its recovery.”
Examining macrophages in the intestines of a handful of people with IBD, the researchers found that a sub-group of cells responding to prostaglandin E2 (PGE2). Prostaglandins are messenger molecules involved in homeostatic functions and mediate pathogenic mechanisms, such as the inflammatory response, and are also involved in tissue repair.
“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. This suggests that they are part of the reparative process,” said Professor Gianluca Matteoli, immunologist, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven
In mice with ulcerative colitis (one the main forms of IBD), there were fewer macrophages responsive to prostaglandin than in healthy mice. However, when PGE2 levels were increased, those macrophages still responsive released a substance that stimulated tissue repair. When the researchers knocked out the PGE2 receptors on the macrophages, the level of tissue repair dropped.
Getting the macrophages to absorb a liposome containing a substance to trigger the repair stimulation agent restored the macrophages’ repairing effect. Liposomes are bubbles made of two layers of lipids enclosing an aqueous cavity, often used to hold substances for drug delivery.
“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,” Professor Matteoli said.
New treatments could involve liposomes being used to prompt macrophages into boosting tissue repair, a well-established experimental tool but which would require considerable work for this new application.
“This is one of the first times it has been used to produce a beneficial, therapeutic effect,” said Professor Seok.
The next step is to closely examine human macrophages at different stages of IBD. “We want to identify other factors that trip the switch that turns macrophages from inflammatory cells to non-inflammatory cells,” said Professor 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.”
Source: News-Medical.Net
