Contrasting models for the roles of Aire in the differentiation program of epithelial cells in the thymic medulla

The current prevailing view regarding the role of Aire in self-tolerance is that it is involved in the transcriptional control of many tissue-restricted self-antigen genes in thymic epithelial cells in the medulla (mTECs); however, accumulating evidence also suggests that Aire has other roles, e.g. in mTEC differentiation, and furthermore that Aire can either promote or inhibit the mTEC differentiation program, i.e. Aire does not play a neutral role in mTEC differentiation. This review discusses when and how Aire plays an important role in controlling the organization of mTECs required for the expression of self-antigen genes.