AIRE and immunological tolerance: insights from the study of autoimmune polyendocrinopathy candidiasis and ectodermal dystrophy.
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.
Notarangelo
Luigi D
LD
Department of Pediatrics and Angelo Nocivelli Institute of Molecular Medicine, Children's Hospital, University of Brescia, 25123 Brescia, Italy. notarang@med.unibs.it
Mazza
Cinzia
C
Forino
Concetta
C
Mazzolari
Evelina
E
Buzi
Fabio
F
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
D014157:Transcription Factors; D000096927:AIRE Protein