MSGID: 1:317/3 642cf97d   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Study to decode microbe-gut signaling suggests potential new treatment   
   for IBD    
    Harmful intestinal inflammation might be prevented with a one-two punch   
      
      
     Date:   
         April 4, 2023   
     Source:   
         Cincinnati Children's Hospital Medical Center   
     Summary:   
         Fresh insights into how our bodies interact with the microbes   
         living in our guts suggest that a two-drug combination may offer   
         a new way to treat inflammatory bowel diseases such as Crohn's   
         disease and ulcerative colitis.   
      
      
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   FULL STORY   
   ==========================================================================   
   Fresh insights into how our bodies interact with the microbes living   
   in our guts suggest that a two-drug combination may offer a new way to   
   treat inflammatory bowel diseases such as Crohn's disease and ulcerative   
   colitis.   
      
      
   ==========================================================================   
   The potential treatment pathway emerges from a study led by experts at   
   Cincinnati Children's published online March 28, 2023, in the Journal of   
   Experimental Medicine. Co-first authors were Garrett Overcast, PhD, and   
   Hannah Meibers, BS. Corresponding author was Chandrashekhar Pasare, DVM,   
   PhD, Division of Immunobiology and co-director, Center for Inflammation   
   and Tolerance.   
      
   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 scrambled --   
   by genetic mutations or other causes such as damage to the intestinal   
   epithelium -- the 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 says. "We believe this may help explain why past   
   treatments for IBD that focused only on inhibiting IL-1? 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."  What's next?   
   Some monoclonal antibodies that can inhibit IL-22 or IL-1R have been   
   evaluated in clinical trials for various auto-immune conditions. The   
   research team is interested in exploring whether existing products can be   
   safely used in combination therapy or whether developing new treatments   
   that target the two pathways would be more effective.   
      
   Cincinnati Children's co-authors for this publication also included Emily   
   Eshleman, PhD, Irene Saha, PhD, Lisa Waggoner, MS, Krupaben Patel, BS,   
   David Haslam, MD, Theresa Alenghat, VMD, PhD, and Kelli VanDussen, PhD;   
   and Viral Jain, MD, University of Alabama at Birmingham.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Immune_System # Colitis # Gastrointestinal_Problems   
                   # Lymphoma   
             o Plants_&_Animals   
                   # Genetics # Molecular_Biology # Biology # Biotechnology   
       * RELATED_TERMS   
             o Microorganism o Irritable_bowel_syndrome o Pharmacology   
             o Ketone_bodies o Coeliac_disease o Chemotherapy o   
             Personalized_medicine o Prion   
      
   ==========================================================================   
   Story Source: Materials provided by   
   Cincinnati_Children's_Hospital_Medical_Center. Note: Content may be   
   edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Garrett R. Overcast, Hannah E. Meibers, Emily M. Eshleman,   
      Irene Saha,   
         Lisa Waggoner, Krupaben N. Patel, Viral G. Jain, David   
         B. Haslam, Theresa Alenghat, Kelli L. VanDussen, Chandrashekhar   
         Pasare. IEC-intrinsic IL-1R signaling holds dual roles in regulating   
         intestinal homeostasis and inflammation. Journal of Experimental   
         Medicine, 2023; 220 (6) DOI: 10.1084/jem.20212523   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/04/230404114152.htm   
      
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