These results, together with our previous work showing that both Smad7 knockdown and activation of Sirt1 attenuate intestinal inflammation (5, 10), help delineate a scenario in which, in IBD mucosa, high Smad7 contributes to reduce Sirt1 content with the downstream effect of attenuating negative effects on its own expression and amplifying tissue-damaging immune responses. Here, SMAD7 is linked to inflammatory bowel disease.