title: Alterations of the autoimmune regulator transcription factor and failure of central tolerance: APECED as a model.
abstract: Self-nonself discrimination plays a key role in inducing a productive immunity and in preventing autoimmune reactions. Central tolerance within the thymus and peripheral tolerance in peripheral lymphoid organs lead to immunologic nonresponsiveness against self-components. The central tolerance represents the mechanism by which T cells binding with high avidity to self-antigens are eliminated through the so-called negative selection. Thymic medullary epithelial cells and medullary dendritic cells play a key role in this process, through the expression of a large number of tissue-specific self-antigens involving the transcription factor autoimmune regulator (AIRE). Mutations of AIRE result in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, a rare autosomal recessive disease (OMIM 240300), which is the paradigm of a genetically determined failure of central tolerance and autoimmunity. This review focuses on recent advances in the molecular mechanisms of central tolerance, their alterations and clinical implication.
authors.affiliation: Department of Pediatrics, Federico II University, S Pansini 5, 8013 Naples, Italy.
authors.forename: Vera
authors.initials: V
authors.lastname: Gallo
authors.forename: Giuliana
authors.initials: G
authors.lastname: Giardino
authors.forename: Donatella
authors.initials: D
authors.lastname: Capalbo
authors.forename: Loredana
authors.initials: L
authors.lastname: Palamaro
authors.forename: Rosa
authors.initials: R
authors.lastname: Romano
authors.forename: Francesca
authors.initials: F
authors.lastname: Santamaria
authors.forename: Filomena
authors.initials: F
authors.lastname: Maio
authors.forename: Mariacarolina
authors.initials: M
authors.lastname: Salerno
authors.forename: Pietro
authors.initials: P
authors.lastname: Vajro
authors.forename: Claudio
authors.initials: C
authors.lastname: Pignata
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D006801:Humans; D007108:Immune Tolerance; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D000096927:AIRE Protein
chemical_list: D001324:Autoantigens; D014157:Transcription Factors; D000096927:AIRE Protein