Crohn’s Disease May Develop from Altered Immune Cell Signaling During Bile Acid Exposure; Study Published in Nature Reveals How T Cells in Small Intestine Respond to Bile Acids, Offering Localized Treatment Direction for a Cause of Chronic Illness

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, Associate Professor in the Department of Immunology and Microbiology at Scripps Research, Florida, suggests a more targeted treatment approach is possible. Crohn’s disease develops from chronic inflammation in the digestive tract, often the small intestine. 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 an article published online on April 7, 2021 in Nature, Dr. 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 in the small intestine. This sensory mechanism can be manipulated with small drug-like molecules, they find, and the treatment reduced small bowel inflammation in mice. The Nature article is titled “CAR Directs T Cell Adaptation to Bile Acids in the Small Intestine” (https://www.nature.com/articles/s41586-021-03421-6). “It seems that these immune cells, called T effector cells, have learned how to protect themselves from bile acids,” Dr. Sundrud says. “These T cells utilize an entire network of genes to interact safely with bile acids in the small intestine. This pathway may malfunction in at least some individuals with Crohn’s disease.”
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