MSGID: 1:317/3 6430eddf   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Study sheds light on how IBD can develop    
    Gene loss weakens antibacterial defense in inflammatory bowel disease in   
   mouse study    
      
     Date:   
         April 7, 2023   
     Source:   
         University of California - Riverside   
     Summary:   
         A new study could help improve personalized medicine approaches   
         in inflammatory bowel disease by understanding how patients with   
         variants in the PTPN2 gene develop IBD.   
      
      
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   FULL STORY   
   ==========================================================================   
   Inflammatory bowel disease, or IBD, describes Crohn's disease and   
   ulcerative colitis, two chronic diseases that cause inflammation in the   
   intestines. IBD, which affects about 3 million adults in the United   
   States, is an autoimmune disorder -- a condition in which the body's   
   immune system attacks healthy tissues. Its symptoms include diarrhea,   
   rectal bleeding, fatigue, weight loss, and stomach cramps.   
      
      
   ==========================================================================   
   The intestinal epithelium, made up of a layer of cells that lines the   
   intestine, plays an important role in IBD because it can be easily   
   disrupted during gut inflammation. A specialized type of epithelial   
   cells are Paneth cells. The antimicrobial peptides these cells produce   
   help regulate the gut microbiota, or the community of microorganisms   
   that exist in the gut.   
      
   A research team led by Declan F. McCole, a biomedical scientist and IBD   
   expert at the University of California, Riverside, reports in their mouse   
   study that reduced activity of the IBD risk gene PTPN2 in intestinal   
   epithelial cells can lead to a decrease in the production of Paneth cell   
   antimicrobial peptides.   
      
   The study, published in the journal Cellular and Molecular   
   Gastroenterology and Hepatology, establishes a critical link between   
   PTPN2 and Paneth cells that plays a major role in maintaining normal   
   gut microbe properties.   
      
   "This study develops our focus on improving personalized medicine   
   approaches in IBD by understanding how patients with variants in the   
   PTPN2 gene develop IBD," said McCole, a professor of biomedical sciences   
   in the School of Medicine.   
      
   "Loss of PTPN2 can lead also to selective loss of Paneth cells in the   
   intestinal epithelium. This loss of PTPN2 causes significant changes in   
   the gut microbiota and increases a particular E. coli."  Escherichia coli,   
   or E. coli, are bacteria found in the environment, foods, and intestines   
   of people and animals. McCole explained that the E. coli in question,   
   the adherent-invasive E. coli, or AIEC, is increased in IBD and worsens   
   inflammation. First identified in Crohn's disease patients, AIEC can   
   adhere to and invade epithelial cells as well as immune cells called   
   macrophages.   
      
   "AIEC are the strongest candidate for a causal role for bacteria in IBD,"   
   he said.   
      
   According to McCole, Paneth cells do not function properly in many   
   patients living with IBD, and this can serve as a marker of disease. The   
   antimicrobial peptides these cells produce are crucially relevant to the   
   intestine's protective barrier for regulating the relative proportions   
   of bacteria and their interactions with each other. They also help   
   neighboring intestinal stem cells function better.   
      
   "We know that in IBD, Paneth cells are often unable to produce sufficient   
   antimicrobial peptides or respond appropriately to gut bacteria,"   
   McCole said.   
      
   "These functional defects can also be associated with changes in   
   the structure of Paneth cells that reduce their ability to secrete   
   the protective antimicrobial peptides, leading to increases in the   
   populations of bacteria associated with IBD, such as AIEC. These   
   structural changes in the appearance of Paneth cells can also serve as a   
   marker of disease in IBD, especially Crohn's disease."  McCole was joined   
   in the study by Vinicius Canale, Marianne R. Spalinger, Rocio Alvarez,   
   Anica Sayoc-Becerra, Golshid Sanati, Salomon Manz, Pritha Chatterjee,   
   Alina N. Santos, Hillmin Lei, Sharon Jahng, Timothy Chu, and Ali Shawki   
   of UCR; Elaine Hanson and Lars Eckmann of UC San Diego; and Andre'   
   J. Ouellette of the University of Southern California.   
      
   The study was supported by the Crohn's and Colitis Foundation; Swiss   
   National Science Foundation; American Gastroenterological Association;   
   Science Without Borders Program; and California Institute of Regenerative   
   Medicine.   
      
   "This work sets the foundation for our new research project that will   
   identify pharmacologic agents capable of rescuing Paneth cell function   
   and reducing the contributions of microbes to intestinal inflammation,"   
   McCole said.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Gastrointestinal_Problems # Colitis # Immune_System   
                   # Crohn's_Disease # Stem_Cells # Lymphoma #   
                   Diseases_and_Conditions # Hearing_Loss   
       * RELATED_TERMS   
             o Personalized_medicine o Irritable_bowel_syndrome o   
             Vector_(biology) o Alternative_medicine o Rheumatic_fever o   
             Gene_therapy o Alzheimer's_disease o Medicine   
      
   ==========================================================================   
   Story Source: Materials provided by   
   University_of_California_-_Riverside. Original written by Iqbal   
   Pittalwala. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Vinicius Canale, Marianne R. Spalinger, Rocio Alvarez, Anica Sayoc-   
         Becerra, Golshid Sanati, Salomon Manz, Pritha Chatterjee, Alina N.   
      
         Santos, Hillmin Lei, Sharon Jahng, Timothy Chu, Ali Shawki, Elaine   
         Hanson, Lars Eckmann, Andre' J. Ouellette, Declan F. McCole. PTPN2   
         is a Critical Regulator of Ileal Paneth Cell Viability and Function   
         in Mice.   
      
         Cellular and Molecular Gastroenterology and Hepatology, 2023;   
         DOI: 10.1016/j.jcmgh.2023.03.009   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/04/230407133533.htm   
      
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