Linking signalling pathways, thymic stroma integrity and autoimmunity

Medullary thymic epithelial cells (mTECs) are indispensable for self-tolerance to peripheral organs by virtue of their expression of a host of tissue-restricted self-antigens. The full extent of this promiscuous gene expression is confined to functionally mature mTECs. Consequently, any interference with signalling pathways directing the differentiation and/or proliferation of this mature subset will affect the scope of central tolerance and potentially predispose to autoimmunity. In a recent study, tumour necrosis factor receptor-associated factor 6 (TRAF6) has been identified as an essential component of a new signalling pathway directing mTEC development.