Gut tissue may retain inflammatory 'memory' for more than a year
Every three to five days, the layer of cells lining our intestines is completely renewed—the fastest turnover rate in the human body. Such rapid regeneration is an absolute necessity for tissue that endures constant mechanical stress as well as an abundance of bacteria and contaminants. But what happens to the "glue" that holds these cells together? Does it, too, recover quickly from damage?
A new study published in Immunity by researchers at the Weizmann Institute of Science reveals that gut tissue may retain inflammatory memory for more than a year. The layer of cells lining our intestines is renewed every three to five days, but the material between these cells, known as the extracellular matrix or ECM, can retain the effects of inflammation long after the tissue has healed.
This persistence of inflammatory memory, rather than immune cells and their secretions, is a novel focus of research in the Sagi lab. Previous findings from this lab demonstrated that changes in the intestinal ECM could diagnose inflammatory bowel disease early. The new study shows that severe initial damage to the intestinal epithelial cells can alter the ECM irreversibly, preventing normal regeneration and leading to chronic inflammatory bowel diseases like Crohn's disease and ulcerative colitis.
Chronic inflammation can develop following transient intestinal damage, often triggered by factors like medications, stress, or smoking. The researchers used mouse models to observe the lasting effects of acute intestinal inflammation for over a year. Despite the intestine recovering, the ECM failed to regenerate properly, remaining distorted and porous for up to 400 days.
By growing stem cells on damaged ECM, researchers found that these cells matured into inflammation-promoting epithelial cells instead of normal intestinal cells. These pro-inflammatory epithelial cells were also found in inflamed regions of patients with ulcerative colitis, suggesting the ECM's critical role in chronic inflammation.
The study identifies collagen 18 as a protein responsible for rewiring stem cells during chronic inflammation, marking it as a potential early indicator of the disease.
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