Objectives

We ask whether dysregulation in the gene expression that occurs in the thymus gland could be associated to onset of aggressive autoimmunity. The thymic stromal cells (mTECs) are highlighted in our current projects since these cells feature a peculiar program in their gene expression: they ectopically express virtually all peripheral tissue antigens (PTAs) genes characterizing all organs and systems of the body. This phenomenon is termed promiscuous gene expression (PGE), which is transcriptionally controlled by the autoimmune regulator (Aire) and forebrain-expressed zinc finger 2 (Fezf2) genes. This process is implicated in the self-representation of PTAs by mTECs to developing thymocytes within the thymus eliminating those clones of self-reactive cells (negative selection). Our working hypothesis is that dysregulation of PGE, either at transcriptional (involving the Aire gene) or at posttranscriptional level (involving miRNAs), might be implicated in the lack of immune tolerance.