SMAD3 and cancer: In contrast to the disease-promoting role of the dysregulated immune response in Smad3−/− mice, our data also demonstrate that adaptive immune cells play a protective, SMAD3-independent role in DSS-induced disease as Smad3−/− mice lacking T and B cells (Smad3/Rag-DKO mice) developed increased DSS-induced inflammation and cancer compared to T and B cell sufficient Smad3−/− mice.