Peripheral Aire

Extrathymic cells that express the transcriptional regulator Aire (eTACs) have been described, but their role in immunotolerance is unclear. In Immunity, Anderson and colleagues show that eTACs are radioresistant, bone marrow–derived MHCII^hiCD80^loCD86^loEpCAM^hiCD45^lo antigen-presenting cells (APCs) present in the secondary lymphoid organs of mice and humans. eTACs interact with CD4⁺ T cells and induce immunotolerance via functional inactivation of interacting T cells and independently of the induction of regulatory T cells. T cells tolerized by eTACs have impaired TCR signaling, probably as a result of engagement of the TCR in the absence of effective costimulation. These findings show that Aire expression can induce tolerance in peripheral lymphoid organs.

Immunity 39, 560–572 (2013)