SMAD3 and colitis: However, Treg cells incapable of responding to TGF-β signaling via the expression of a dominant-negative TGF-β receptor type II (Fahlén et al., 2005), depletion of TGF-β receptor II (Sledzińska et al., 2013), or deficiency in the downstream TGF-β signaling molecule Smad3 (Kullberg et al., 2005) are still able to suppress T-cell-mediated colitis, in contrast to the inability of T cells that cannot sense TGF-β to be suppressed by Treg cells (Fahlén et al., 2005).