Transcriptional impact of Aire varies with cell type.

Abstract

Aire promotes T cell tolerance by inducing the expression of a broad swath of genes encoding peripheral tissue antigens (PTAs) in medullary epithelial cells (MECs) of the thymus. The exact mechanism used in inducing this ectopic transcription remains obscure. To address this issue, we generated transgenic mice expressing Aire in pancreatic islet beta cells. Gene-expression profiling of such islets revealed that Aire can have a significant impact on transcription in these cells, mainly inducing, but also repressing, transcript levels in a manner comparable with its influence on MECs. The exact transcripts affected differed in MECs and beta cells, with limited overlap between the two sets of Aire-modulated genes. We propose that Aire promotes ectopic gene expression by a generic mechanism that does not depend on any particular characteristics or transcription mechanisms operating in MECs, whereas the cellular environment does govern which genes are actually susceptible to Aire regulation.