Several factors, including retinoic acid, have been shown to enhance the TGF-β/Smad3-dependent induction of Treg cells (Xiao et al, 2008), which highlights the importance of the TGF-β/Smad3 pathway in Treg cell-mediated immune homeostasis and the therapeutic potential of manipulating this pathway to treat autoimmune diseases. This evidence concerns the gene SMAD3 and autoimmune disease.