Caspase activation and recruitment domain 3 (CARD3) is a 61-kDa protein kinase. Recent evidence shows the importance of CARD3 in the immune response and inflammatory diseases. To elucidate its impact on inflammatory bowel disease, we studied the effects of the loss of CARD3 in the acute dextran sodium sulfate-induced colitis.Colitis was induced by administration of dextran sodium sulfate to wild-type and CARD3 mice. Colon tissues were analyzed.CARD3 mice were less susceptible to the development of colitis than wild-type controls as determined by weight loss, disease activity, colon histology, neutrophil infiltration, and cytokine expression. Reduced susceptibility of CARD3 mice to colitis was closely related to increased density of colonic epithelial cells relative to wild-type controls, which was because of decreased levels of apoptosis that resulted in enhanced epithelial barrier function. Finally, CARD3 levels were increased in intestinal tissue from patients with IBD.These results imply a role for CARD3 as a positive regulator of intestinal epithelial cell apoptosis in the inflamed colon. Genetic loss of CARD3 is protective against colitis through decreased epithelial cell apoptosis and consequent enhancement of intestinal epithelial barrier function. Thus, targeted CARD3 inhibition may represent a new therapeutic approach in IBD.
