SMAD3 and autoimmune disease: Speaking of the antagonism of the two cytokines in their respective pathways, the increase of TNF-α can lead to the activation of AKT, and activated AKT can interact with Smad3, which leads to the inhibition of TGF-β pathway in regulatory T cells, so TNF-α can weaken the differentiation and function of Treg cells induced by TGF-β in autoimmune diseases through AKT and Smad3 signaling pathways (66).