Cincinnati [United States], April 4 : Inflammatory bowel diseases like Crohn's disease and ulcerative colitis may soon be treated with a two-drug combination, according to recent discoveries about how our systems interact with the bacteria that live in our guts.
A study conducted at Cincinnati Children's and published in the Journal of Experimental Medicine reveals the potential therapeutic route. Garrett Overcast, PhD, and Hannah Meibers, BS, shared first authorship. Chandrashekhar Pasare, DVM, PhD, co-director of the Institute for Inflammation and Tolerance, served as the corresponding author.
The research team conducted numerous experiments to learn about how immune cells located in the lining of the intestine detect and respond to microbes and relay important signals to gut epithelial cells. When the signaling networks between immune cells and epithelial cells function correctly, the immune system can live in harmony with friendly bacteria residing in the gut.
Acting in unhealthy concert
When microbe-to-cell signals get scrambledby genetic mutations or other causes such as damage to the intestinal epitheliumthe immune system can either fail to react or can over-react, which can lead to inflammatory bowel disease (IBD).
This study reveals that microbes are detected by cells of the immune system located in the intestines. These immune cells deliver signals to induce a protein called IL-1. This increases levels of another protein called IL-22, which in turn, begins acting in concert with IL-1 to activate the IL-1 receptor (IL-1R) expressed on intestinal epithelial cells. Activation of IL-1R induces ROS gene activity in addition to other genes that recruit inflammatory cells to the tissue. This chain reaction drives an excessive inflammatory response that can damage the intestine, the researchers say.
"The pathogenic role that IL-22 appears to play in inflammatory responses - due to its synergy with IL-1R signaling - had not been made clear previously," Pasare said. "We believe this may help explain why past treatments for IBD that focused only on inhibiting IL-1b activity had mixed results. We believe that a combined blockade of both IL-22 and IL-1R could serve as a more promising treatment for IBD."
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