IEX-1 may be a target for prevention of colitis and colon cancer

Inflammatory bowel disease (IBD) is initiated by uncontrolled inflammation in the colon mucosal areas, triggered by normal intestinal microflora.  In the United States, an estimated 1.4 million subjects suffer from IBD, with about 30,000 new cases reported each year.  No cure for this disorder is available at this time.  The remission can be induced and, in some cases, maintained with a number of medications. 

These medications treat the symptoms through general reduction and/or suppression of the entire immune system, thus often causing side-effects.  Therefore, there is an urgent need for new biological therapies that could selectively target a particular molecule.  IEX-1 KO mice are refractory to dextran sulfate sodium (DSS)-induced colitis, a widely used mouse model to study human ulcerative colitis, in part due to enhanced apoptosis of activated T cells that limits colon inflammation, and augmented Th17 cell differentiation that protects the integrity of colon epithelial barrier. 

In accordance with reduced colon inflammation, IEX-1 KO mice also developed a significantly fewer colorectal tumors induced by azoxymethane (AZO)/repetitive DSS administration.  Thus, inhibition of IEX-1 expression may be a novel strategy to prevent colitis and colon cancer.