title: Disruption of immunological tolerance: role of AIRE gene in autoimmunity.
abstract: The mechanism underlying the generation of T and B autoreactive clones in autoimmune diseases is still unknown. Among genetic factors implicated in autoimmunity, Autoimmune Regulator gene (AIRE) is one of the candidates to better understand the complex scenario of autoimmune manifestations. AIRE mutations are responsible for the development of autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) with monogenic autosomal recessive inheritance; it has been shown that AIRE regulates the negative selection of autoreactive T cells clones, driving the transcription of tissue-specific antigens in thymic epithelial cells. In various autoimmune manifestations correlated or not to APECED, AIRE variants act in a semidominant manner, leading to a reduction in AIRE protein amount per cell, and consequently to a marked decrease in ectopic proteins expression in the thymus. The co-occurrence of autoimmune diseases in the same individual has prompted several studies aimed to recognize shared patho-physiological mechanisms; in this scenario small reductions in function could explain the predisposition to autoimmunity in AIRE-heterozygous carriers of missense mutations; further studies to investigate whether the AIRE gene is involved in determining these autoimmune manifestations should be carried out.
authors.affiliation: Center of Excellence for Biomedical Research, University of Genoa, Italy. rizzi.marta@libero.it
authors.forename: M
authors.initials: M
authors.lastname: Rizzi
authors.forename: F
authors.initials: F
authors.lastname: Ferrera
authors.forename: G
authors.initials: G
authors.lastname: Filaci
authors.forename: F
authors.initials: F
authors.lastname: Indiveri
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D009154:Mutation / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein