Research has shown that TOB1 interacts with the TGF (transforming growth factor) and can stimulate transcription factors SMAD4 and SMAD2, increasing their binding to the IL-2 promoter and helping to repress IL-2 expression, suggesting that interference in TOB1 function be associated with autoimmune disease (Tzachanis et al., 2001; Tzachanis and Boussiotis, 2009; Gibson, 2010). This evidence concerns the gene SMAD4 and autoimmune disease.