title: AIRE and immunological tolerance: insights from the study of autoimmune polyendocrinopathy candidiasis and ectodermal dystrophy.
abstract: OBJECTIVE
  To review the clinical and molecular features of autoimmune polyendocrinopathy candidiasis and ectodermal dystrophy and discuss recent advances in the function of the AIRE protein. We will summarize how AIRE contributes to immunological tolerance, and thus to the prevention of autoimmunity.
  
  
  RESULTS
  The organization of a well-structured thymic microenvironment and the interaction between nascent thymocytes and thymic epithelial cells have been shown to be essential for AIRE expression. AIRE is involved in the expression of ectopic proteins by medullary thymic epithelial cells. This allows the establishment of central tolerance and contributes to the prevention of organ-specific autoimmunity, as shown by findings in patients with autoimmune polyendocrinopathy candidiasis and ectodermal dystrophy (a disease caused by AIRE gene mutations) and in aire (-/-) mice.
  
  
  CONCLUSIONS
  Autoimmune polyendocrinopathy candidiasis and ectodermal dystrophy represents a unique model to investigate the cellular and molecular mechanisms that govern central tolerance and help prevent autoimmunity. Recent findings indicate that the compartmentalization of AIRE and interaction with other proteins are involved in this mechanism. The disturbance of AIRE expression may also be responsible for autoimmune manifestations in disorders with disrupted thymic structure other than autoimmune polyendocrinopathy candidiasis and ectodermal dystrophy alone.
authors.affiliation: Department of Pediatrics and Angelo Nocivelli Institute of Molecular Medicine, Children's Hospital, University of Brescia, 25123 Brescia, Italy. notarang@med.unibs.it
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Cinzia
authors.initials: C
authors.lastname: Mazza
authors.forename: Concetta
authors.initials: C
authors.lastname: Forino
authors.forename: Evelina
authors.initials: E
authors.lastname: Mazzolari
authors.forename: Fabio
authors.initials: F
authors.lastname: Buzi
mesh_terms: D002177:Candidiasis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004476:Ectodermal Dysplasia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein