Immunoendocrinology: Scientific and Clinical Aspects

Abstract

Autoimmune polyglandular syndrome type 1 (APS-1) is a monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Here we describe the mouse models of APS-1 generated by targeted mutation of the mouse Aire gene, and how these models recapitulate the autoimmunity seen in APS-1. Further, we discuss how the study of these mouse systems has shed light on the pathogenesis of the disease and some of the basic mechanisms of self-tolerance in the immune system. Aire promotes self-antigen expression within the thymus, and failure to express such antigens in the thymus leads to autoimmunity. We discuss how the AIRE protein may function at a molecular and cellular level to accomplish this remarkable feat. We then address the identification of organ-specific antigens and the characterization of specific cell populations involved in this disease model, and how these discoveries in the mouse may lead to improved therapies for APS-1 and other autoimmune diseases. Finally, we present a number of current and prospective topics in autoimmunity and self-tolerance that have emerged from the study of these mouse models.