Researchers at the UCR School of Medicine recently made a breakthrough discovery in their study of Inflammatory Bowel Disease (IBD) and the different causes of inflammation. The team, led by Distinguished Professor of Biomedical Sciences Dr. David Lo, discovered that the same cells that cause inflammation could also potentially provide healing to the digestive tract as well. With this new information, the researchers hope to create a medication that better treats patients plagued by chronic inflammation and to better understand how the mucosal immune system works.
IBD is a chronic inflammatory condition that afflicts the intestines. Included under IBD is ulcerative colitis and Crohn’s disease, which plagues more than two million Americans. Current medications that are commonly prescribed are effective less than half the time, which Lo and his team hope to address.
Lo suggests that the field of research he and his team are operating in is difficult because the tools to study M cells and the mucosal immune system are so few. Lo explained, “The underlying problem is that we don’t know what drives the process in inflammatory bowel disease.”
Lo and his team of researchers sought to discover why only half of patients treated with “biologicals that block tumor necrosis factor alpha (TNF-alpha)” get long-term benefits. TNF-alpha is a protein that notifies the immune system of foreign contaminants and produces inflammation in response. Using a mouse model, the researchers tested potential therapeutics by giving the mice “a bacterial infection that mimics many of the diseases’ effects and another in which they are fed a compound that causes inflammation in the gut so that it also resembles a lot of the physical aspects of the disease.” After evaluation of the mice’s responses to the therapeutics, they found a “definite change in the way the mucosal immune system is activated in these diseases” using M cells.
M cells are used to detect when bacteria or viruses are in the gut and notify the immune system by “carrying it across the barrier of the gut and presenting it to cells in the immune system,” but infectious diseases like salmonella and anthrax also take advantage of the role of the M cells and then infect the immune system.
Additionally, they discovered that M cells are created in the gut and are trying to further determine the role M cells play in the disease. Lo suspects that “millions of years of evolution created a system for generating new M cells, probably for a good reason, so that you can activate more immunoregulatory mechanisms to help suppress the response.” This, however, is completely dependent upon the production of TNF, which the team found to both induce and “promote healing and regulatory aspects.”
In their most recent reports, the team found that tumor necrosis factor receptor 2 (TNFR2) is the receptor responsible for the induction of the M cells. Currently, the drugs on the market used to treat IBD block all TNF, potentially preventing inflammation but also blocking the production of M cells which promote healing. Lo said they seek to address whether “a non-selective TNF blockade is so nonspecific that it is blocking both the inflammatory, as well as the healing response (of M cells). That is a tricky question because there are no drugs on the market that are selective for one or the other. The work that we have so far suggests that maybe our next step in development needs to be selective blockade.”