The autoimmune regulator: a key toward understanding the molecular pathogenesis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autoimmune disease with autosomal recessive inheritance. APECED is characterized by the breakdown of tolerance to several organ-specific selfantigens. The symptoms of APECED fall into three main categories: autoimmune polyendocrinopathies, chronic mucocutaneous candidiasis, and ectodermal dystrophies. The gene defective in APECED, AIRE, has been cloned and numerous mutations in this gene have been found in patients with APECED. AIRE is predicted to encode a 545-amino-acid protein containing structural domains characteristic for transcription regulators. The protein has been shown to act as a transcriptional activator in vitro. The AIRE protein is mainly localized to the nucleus, where it can be detected as speckles resembling nuclear bodies. In humans, the expression of AIRE has been observed predominantly in immunologically relevant tissues, especially the thymus. Recently, we have shown in the mouse that Aire is also expressed in various tissues and cell types outside the immune system.
Meriluoto
T
T
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland. tanja.meriluoto@ktl.fi
Halonen
M
M
Pelto-Huikko
M
M
Kangas
H
H
Korhonen
J
J
Kolmer
M
M
Ulmanen
I
I
Eskelin
P
P
D000818:Animals; D005260:Female; D015870:Gene Expression; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000096927:AIRE Protein
D014157:Transcription Factors; D000096927:AIRE Protein