One of the hallmarks of the adaptive immune system is its ability to distinguish between self and nonself, in order to be able to protect the individual from invading pathogens, while avoiding a potentially-destructive immune response against the body’s own tissues. Collectively known as immune tolerance, this ability is governed by an array of tightly regulated processes that are at the heart of immunological research. Much of our understanding of the mechanisms underlying immune tolerance has come from studying various cases of autoimmune disorders, which occur as a consequence of breakdown of self-tolerance mechanisms. Autoimmune polyglandular syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a monogenic autoimmune disorder characterized by devastating multiorgan pathological manifestations. In 1997, two research consortia cloned the gene...
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