Autoimmune Regulator Initiates the Expression of Promiscuous Genes in Thymic Epithelial Cells

Abstract

The expression of peripheral antigens in the thymus, known as promiscuous gene expression, has been implicated in T cell tolerance and autoimmunity. Here we identified thymic epithelial cells (TECs) as the main cell type that expresses a diverse range of tissue-restricted antigens (TRAs). The TECs of a common autoimmune (non-obese diabetic [NOD]) mouse model express much lower levels of an autoimmune regulator (Aire) and TRAs than normal (Balb/c) TECs. Transfection of an Aire plasmid led to increased levels of TRA expression in cultured TECs from Balb/c and NOD mice; an increase that was enhanced by the presence of thymocytes. These data show that Aire initiates promiscuous gene expression in TECs, and that this function might be under thymocyte control.

Keywords:

• Autoimmune regulator
• Promiscuous genes expression
• TECs
• Tissue-restricted antigens

ABBREVIATIONS
PGE,:	=	promiscuous genes expression;
TECs,:	=	thymic epithelial cells;
mTECs,:	=	medullary thymic epithelial cells;
cTECs,:	=	cortical thymic epithelial cells;
TRAs,:	=	tissue-restricted antigens;
Aire,:	=	autoimmune regulator;
TRAs:	=	tissue-restricted antigens
NOD,:	=	non-obese diabetic mice;
Igf2,:	=	Insulin-like growth factor 2;
SP2,:	=	salivary protein 2.