In physiological conditions, the activity of the intestinal immune system is 
tightly regulated to prevent tissue-damaging reactions directed against 
components of the luminal flora. Various factors contribute to maintain immune 
homeostasis and diminished production and/or function of such molecules trigger 
and/or propagate detrimental signals, which can eventually lead to chronic 
colitis and colon cancer. One such a molecule is transforming growth factor-β1 
(TGF-β1), a cytokine produced by many inflammatory and non-inflammatory cells 
and targeting virtually all the intestinal mucosal cell types, with the 
down-stream effect of activating intracellular Smad2/3 proteins and suppressing 
immune reactions. In patients with inflammatory bowel diseases (IBD), there is 
defective TGF-β1/Smad signaling due to high Smad7, an inhibitor of TGF-β1 
activity. Indeed, knockdown of Smad7 with a specific antisense oligonucleotide 
restores endogenous TGF-β1 activity, thereby inhibiting inflammatory pathways in 
patients with IBD and colitic mice. Consistently, mice over-expressing Smad7 in 
T cells develop severe intestinal inflammation in various experimental models. 
Smad7 expression is also upregulated in colon cancer cells, in which such a 
protein controls positively intracellular pathways that sustain neoplastic cell 
growth and survival. We here review the role of TGF-β1 and Smad7 in intestinal 
immunity, inflammation, and cancer.