The Transcriptional Cofactor SKI Regulates Medullary Thymic Epithelial Cell Differentiation and Peripheral T Cell Responses

The thymus is an important site for the establishment and maintenance of an appropriate immune response through positive and negative selection of developing T cells. During selection, developing T cells interact with cortical and medullary thymic epithelial cells (TECs), termed cTECs and mTECs respectively. Our lab found that TEC-specific deletion of Ski decreased the mTEC compartment in the thymus and that tissue restricted antigen (TRA) expression in mTECs was also altered. Interestingly, these mice were significantly protected from developing experimental autoimmune encephalomyelitis (EAE) disease compared to the control mice and naïve CD4 T cells purified from Ski-deleted mice showed a defect in proliferation in vitro after global T cell receptor (TCR) stimulation. Overall, our findings suggest that SKI signaling in the thymus regulates mTEC differentiation and function as well as downstream peripheral T cell responses and provide evidence for targeting SKI in T cell driven autoimmune diseases such as multiple sclerosis.