Study Finds Gut Bacterial Signaling as New Treatment for IBD

A new study from Cincinnati Children’s Hospital Medical Center suggests that blocking IL-22 and IL-1R could offer a promising treatment for IBD.

A recent study conducted by researchers at Cincinnati Children’s Hospital Medical Center, USA, sheds new light on the signaling pathways between immune cells and intestinal epithelial cells in the presence of harmful intestinal inflammation. Research published in Journal of Experimental Medicinemay lead to potential new treatments for inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis.

IBD is a chronic inflammatory disease that affects the gastrointestinal tract and is a major global health problem. Past treatments for IBD have focused on inhibiting IL-1β activity, but these treatments have had mixed results. Potential new pathways have emerged.

The research team conducted a number of experiments to learn how immune cells located in the gut lining detect and respond to microbes and relay important signals to intestinal epithelial cells. When the signaling network between immune cells and epithelial cells functions correctly, the immune system can live in harmony with the friendly bacteria that live in the gut. Unresponsiveness or overreaction can lead to IBD.

The study found that microorganisms are detected by cells immune system located in the intestine. These immune cells transmit signals that induce a protein called IL-1 to raise levels of another protein called IL-22. IL-22 then begins to act in concert with IL-1 to activate the IL-1 receptor (IL-1R) expressed on intestinal epithelial cells. Activation of IL-1R induces activation of ROS genes in addition to other genes that recruit inflammatory cells to tissues. This chain reaction triggers an excessive inflammatory response that can damage the gut, leading to IBD.

“The likely pathogenic role that IL-22 plays in the inflammatory response, due to its synergistic effect with IL-1R signaling, was previously unknown,” said Dr. Chandrashekhar Pasare. , which we believe may help explain why past treatments for IBD that have focused solely on inhibition of IL-1β activity have had mixed results. By doing so, we believe it may serve as a more promising treatment for IBD.”

Control mice demonstrate the ability to clear infections (left column images). However, mice with compromised antimicrobial programs show increased intestinal damage and inflammation (right column images). Journal of Experimental Medicine [Credits: Cincinnati Children’s].

Researchers monoclonal antibody New therapeutics have been developed that can inhibit IL-22 or IL-1R, which are being evaluated in clinical trials in various autoimmune conditions, and can be used safely in combination therapy, or target the two pathways. may occur. The results of this study bring hope for new and effective treatments for his IBD that could improve the quality of life for millions of people around the world.

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