Using a novel transgenic mouse model in which the psoriasis-associated gain-of-function human CARD14(E138A) mutant protein is specifically expressed in IEC, we here show that CARD14 activation in IEC induces increased inflammatory gene expression and immune cell infiltration into the intestinal lamina propria, further suggesting a possible link between dysregulated CARD14 signaling and colitis. Here, CARD14 is linked to colitis.