Abstract
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), formerly known as autoimmune polyendocrine syndrome type 1, is a paradigm of a monogenic autoimmune disease caused by mutations of a gene, named autoimmune regulator (AIRE). AIRE acts as a transcription regulator that promotes immunological central tolerance by inducing the ectopic thymic expression of many tissue-specific antigens. Although the syndrome is a monogenic disease, it is characterized by a wide variability of the clinical expression with no significant correlation between genotype and phenotype. Indeed, many aspects regarding the exact role of AIRE and APECED pathogenesis still remain unraveled. In the last decades, several studies in APECED and in its mouse experimental counterpart have revealed new insights on how immune system learns self-tolerance. Moreover, novel interesting findings have extended our understanding of AIRE’s function and regulation thus improving our knowledge on the pathogenesis of APECED. In this review, we will summarize recent novelties on molecular mechanisms underlying the development of APECED and their clinical implications.
Highlights
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), formerly known as autoimmune polyendocrine syndrome type 1 (APS-1), is a rare disease caused by mutations of the autoimmune regulator (AIRE) which acts as a transcription regulator that promotes immunological central tolerance [1]
Recent advances on how AIRE affects immunological tolerance and is linked to organ-specific autoimmunity have improved our understanding on the pathogenesis and the wide variability of clinical expression of APECED
Medullary thymic epithelial cells have a primary role in the negative selection and, in this context, AIRE acts as a crucial transcriptional regulator
Summary
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), formerly known as autoimmune polyendocrine syndrome type 1 (APS-1), is a rare disease caused by mutations of the autoimmune regulator (AIRE) which acts as a transcription regulator that promotes immunological central tolerance [1]. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy represents a paradigm of genetically determined systemic autoimmunity. The great variability that characterizes APECED, irrespectively of AIRE genotype, implies that additional factors modulate the clinical expression of the disease. Recent advances on how AIRE affects immunological tolerance and is linked to organ-specific autoimmunity have improved our understanding on the pathogenesis and the wide variability of clinical expression of APECED. We will summarize new insights into AIRE genetics and functioning and its implications on APECED phenotype
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