Study offers localized treatment direction for a cause of Crohn’s disease

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Sumary of Study offers localized treatment direction for a cause of Crohn’s disease:

  • People with Crohn’s disease are typically treated with powerful anti-inflammatory medications that act throughout their body, not just in their digestive tract, creating the potential for unintended, and often serious, side effects..
  • New research from the lab of Mark Sundrud, PhD, at Scripps Research, Florida suggests a more targeted treatment approach is possible..
  • More than half a million people in the United States live with the disease, which can be debilitating and require repetitive surgeries to remove irreversibly damaged intestinal tissue..
  • Writing in the journal Nature on April 7, Sundrud’s team finds that certain immune cells in the small intestine have evolved a molecular sensing mechanism to protect themselves from the toxic effects of high bile acid concentrations there..
  • This sensory mechanism can be manipulated with small drug-like molecules, they find, and the treatment reduced small bowel inflammation in mice..
  • They are actively recaptured at the end of the small intestine, in an area called the ileum, where they pass through layers of tissue that contain the body’s dense network of intestinal immune cells, and ultimately re-enter the blood stream for return to the liver..
  • Receptors in the nucleus of both liver cells and intestinal barrier cells sense the presence of bile acid and tell the liver to back off on bile acid production if there’s too much, or to produce more if there aren’t enough to digest a big steak dinner, for example..
  • Given how damaging bile acids can potentially be to cells, scientists have wondered how immune cells that live in or visit the small intestine tolerate their presence at all..
  • Sundrud’s team previously reported that a gene called MDR1, also known as ABCB1, becomes activated when an important subset of immune cells that circulate in blood, called CD4+ T cells, make their way into the small intestine..
  • Related Stories In the new study, Sundrud’s team uses an advanced genetic screening approach to uncover how T cells sense and respond to bile acids in the small intestine to increase MDR1 activity..
  • “The basic discovery that T cells dedicate so much of their time and energy to preventing bile acid-driven stress and inflammation highlights completely new concepts in how we think about and treat Crohn’s disease,”.
  • Acting in the small intestine, CAR promotes expression of MDR1, and also plays a role in activating an essential anti-inflammatory gene, IL-10, the team found..
  • “When we treated mice with drug-like small molecules that activate CAR, the result was localized detoxification of bile acids and reduction of inflammation,”…

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