Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla

The AIRE gene (autoimmune regulator), coding for a putative transcriptional regulatory factor, is mutated in autoimmune-polyendocrinopathy-candidiasis ectodermal dystrophy (APECED). We have investigated the expression of the AIRE gene by mRNA in situ hybridization and immunohistochemistry in various human tissues. Here we show that AIRE is expressed in distinct cells in thymus medulla, and also in rare cells in lymph node paracortex and medulla, and in spleen and fetal liver, but not in the target organs of autoimmune destruction. Double immunofluorescence studies revealed that in thymus medulla both epithelial (cytokeratin positive) and non-epithelial cells expressed AIRE. Subcellularly, AIRE was localised in nuclear dots in thymus and lymph node and also in transfected cells. The cellular localisation of AIRE and its nuclear localisation, compatible with its predicted protein domains, suggest that AIRE may regulate the mechanisms involved in the induction and maintenance of immune tolerance.