A lineage of CD4+ T cells known as Th17 cells, which are derived by exposure of naive CD4+ T cells to IL-6 and TGF-β, have been implicated in several autoimmune diseases. In this issue of the JCI, studies by Acharya et al. and Melton et al. show that TGF-β is activated at the DC/CD4+ T cell synapse by αv integrins and that this activation is required for Th17 differentiation and autoimmunity in the central nervous system. Thus, these studies offer a potential therapeutic target in fighting autoimmune diseases.