Cells lining the intestinal tract form a critical barrier, protecting our bodies from the billions of bacteria living in the gut. Breaches in this barrier are driven largely by a single signaling molecule called tumor necrosis factor (TNF), elevated amounts of which are associated with inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.
Drugs targeting TNF have become an effective treatment against these illnesses, but despite its clinical importance, it is still not clear what triggers an uptick in TNF levels in the gut, or how that event leads to the onset of disease.
Duke researchers have now discovered that a gene called uhrf1 acts like a kind of molecular handbrake on TNF. In the absence of uhrf1, TNF rolls out a series of pro-inflammatory and immune signals that inflame and damage the digestive tract.
These findings provide a new take on how inflammatory bowel diseases can emerge and develop.
The research was published in the Proceedings of the National Academy of Sciences.
