Sterile production of interferons in the thymus

T-cell central tolerance is controlled by thymocyte TCR recognition of self-peptides presented by thymic APCs. While thymic epithelial cells are essential for T-cell central tolerance, a variety of other traditional APCs also play critical roles in T-cell selection. Similar to how peripheral APCs require activation to become effective, thymic APCs also require activation to become tolerogenic. Recent studies have identified IFNs as an essential factor for the activation and generation of an optimally tolerogenic thymic environment. In this review, we focus on interferon (IFN) production within the thymus and its effects on thymic APCs and developing thymocytes. We also examine the importance of T-cell tolerance to IFN itself as well as to interferon-stimulated proteins generated during peripheral immune responses.