title: Recent insights into the role and molecular mechanisms of the autoimmune regulator (AIRE) gene in autoimmunity.
abstract: Since many years immunologists have being tried to answer the tantalizing enigma of immunological tolerance. Complex mechanisms in both thymus (central tolerance) and peripheral lymphoid organs (peripheral tolerance) underly lymphocyte tolerance and its maintenance. The genesis of autoimmunity involves environmental and genetic mechanisms, both contributing to the disruption and deregulation of central and peripheral tolerance, allowing autoreactive pathogenetic T and B-cell clones arising. Among genetic factors the autoimmune regulator (AIRE) gene is one of the best candidates to understand the complex scenario of autoimmunity. Autoimmune polyendocrinopathy syndrome type 1 is a rare autosomal recessive disease caused by mutations in the AIRE gene. Therefore, the disorder has certainly been a powerful model to address the question concerning how a tolerant state is achieved or maintained and to explore how it has gone lost in the context of autoimmunity. AIRE has been proposed to function as a 'non classical' transcription factor, strongly implicated in the regulation of organ-specific antigen expression in thymic epithelial cells and in the imposition of T cell tolerance, thus regulating the negative selection of autoreactive T cell clones. A plethora of proposal have been suggested for AIRE's potential mechanism of action, thus regulating the negative selection of autoreactive T cells. In this review recent discoveries are presented into the role and molecular mechanisms of the AIRE protein in APECED and other autoimmune diseases.
authors.affiliation: Research Laboratories, Children's Hospital Bambino Gesù, Piazza S. Onofrio, 4, 00165 Rome, Italy. fierabracci@opbg.net
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fierabracci
mesh_terms: D000818:Animals; D000941:Antigens / Q000096:biosynthesis / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D009154:Mutation; D009928:Organ Specificity; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000096927:AIRE Protein
chemical_list: D000941:Antigens; D014157:Transcription Factors; D000096927:AIRE Protein