- Betterle, C., Greggio, N. A. & Volpato, M. Autoimmune polyglandular syndrome type I. J. Clin. Endocrinol. Metab. 83, 1049–1055 (1998).
Article CAS Google Scholar
- Leonard, M. Chronic idiopathic hypoparathyroidism with superimposed Addison's disease in a child. J. Clin. Endocrinol. Metab. 6, 493–495 (1946).
Article CAS Google Scholar
- Vogel, A., Strassburg, C. P., Obermayer-Straub, P., Brabant, G. & Manns, M. P. The genetic background of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and its autoimmune disease components. J. Mol. Med. 80, 201–211 (2002).
Article CAS Google Scholar
- Gylling, M. et al. ss-cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J. Clin. Endocrinol. Metab. 85, 4434–4440 (2000).
CAS PubMed Google Scholar
- Halonen, M. et al. AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype. J. Clin. Endocrinol. Metab. 87, 2568–2574 (2002).
Article CAS Google Scholar
- Bjorses, P. et al. Genetic homogeneity of autoimmune polyglandular disease type I. Am. J. Hum. Genet. 59, 879–886 (1996).
CAS PubMed PubMed Central Google Scholar
- Finnish-German APECED Consortium. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nature Genet. 17, 399–403 (1997).
- Nagamine, K. et al. Positional cloning of the APECED gene. Nature Genet. 17, 393–398 (1997).
Article CAS Google Scholar
- Gibson, T. J., Ramu, C., Gemund, C. & Aasland, R. The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor. Trends Biochem. Sci. 23, 242–244 (1998).
Article CAS Google Scholar
- Heino, M. et al. Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem. Biophys. Res. Commun. 257, 821–825 (1999).
Article CAS Google Scholar
- Klamp, T. et al. Expression profiling of autoimmune regulator AIRE mRNA in a comprehensive set of human normal and neoplastic tissues. Immunol. Lett. 106, 172–179 (2006).
Article CAS Google Scholar
- Zuklys, S. et al. Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune- polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). J. Immunol. 165, 1976–1983 (2000).
Article CAS Google Scholar
- Peterson, P. et al. APECED: a monogenic autoimmune disease providing new clues to self-tolerance. Immunol. Today 19, 384–386 (1998).
Article CAS Google Scholar
- Wang, C. Y., Shi, J. D., Davoodi-Semiromi, A. & She, J. X. Cloning of Aire, the mouse homologue of the autoimmune regulator (AIRE) gene responsible for autoimmune polyglandular syndrome type 1 (ASP1). Genomics 55, 322–326 (1999).
Article CAS Google Scholar
- Anderson, M. S. et al. Projection of an immunological self shadow within the thymus by the Aire protein. Science 298, 1395–1401 (2002).
Article CAS Google Scholar
- Anderson, M. S. et al. The cellular mechanism of Aire control of T cell tolerance. Immunity 23, 227–239 (2005).
Article CAS Google Scholar
- Kishimoto, H. & Sprent, J. Negative selection in the thymus includes semimature T cells. J. Exp. Med. 185, 263–271 (1997).
Article CAS Google Scholar
- Kyewski, B. & Klein, L. A central role for central tolerance. Ann. Rev. Immunol. 24, 571–606 (2006).
Article CAS Google Scholar
- Ramsey, C. et al. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum. Mol. Genet. 11, 397–409 (2002).
Article CAS Google Scholar
- Kuroda, N. et al. Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice. J. Immunol. 174, 1862–1870 (2005).
Article CAS Google Scholar
- Jiang, W., Anderson, M. S., Bronson, R., Mathis, D. & Benoist, C. Modifier loci condition autoimmunity provoked by Aire deficiency. J. Exp. Med. 202, 805–815 (2005).
Article CAS Google Scholar
- Liston, A., Lesage, S., Wilson, J., Peltonen, L. & Goodnow, C. C. Aire regulates negative selection of organ-specific T cells. Nature Immunol. 4, 350–354 (2003).
Article CAS Google Scholar
- Derbinski, J. et al. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J. Exp. Med. 202, 33–45 (2005).
Article CAS Google Scholar
- Devoss, J. et al. Spontaneous autoimmunity prevented by thymic expression of a single self-antigen. J. Exp. Med. 203, 2727–2735 (2006).
Article CAS Google Scholar
- Gavanescu, I., Kessler, B., Ploegh, H., Benoist, C. & Mathis, D. Loss of Aire-dependent thymic expression of a peripheral tissue antigen renders it a target of autoimmunity. Proc. Natl Acad. Sci. USA 104, 4583–4587 (2007).
Article CAS Google Scholar
- Liston, A. et al. Gene dosage—limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity. J. Exp. Med. 200, 1015–1026 (2004).
Article CAS Google Scholar
- Niki, S. et al. Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice. J. Clin. Invest. 116, 1292–1301 (2006).
Article CAS Google Scholar
- Kekalainen, E. et al. A defect of regulatory T cells in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J. Immunol. 178, 1208–1215 (2007).
Article Google Scholar
- Andersson, J. et al. The prevalence of regulatory T cells in lymphoid tissue is correlated with viral load in HIV-infected patients. J. Immunol. 174, 3143–3147 (2005).
Article CAS Google Scholar
- Chen, Z., Benoist, C. & Mathis, D. How defects in central tolerance impinge on a deficiency in regulatory T cells. Proc. Natl Acad. Sci. USA 102, 14735–14740 (2005).
Article CAS Google Scholar
- Aschenbrenner, K. et al. Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nature Immunol. 8, 351–358 (2007).
Article CAS Google Scholar
- Heino, M. et al. RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur. J. Immunol. 30, 1884–1893 (2000).
Article CAS Google Scholar
- Kogawa, K. et al. Expression of AIRE gene in peripheral monocyte/dendritic cell lineage. Immunol. Lett. 80, 195–198 (2002).
Article CAS Google Scholar
- Sillanpaa, N. et al. Autoimmune regulator induced changes in the gene expression profile of human monocyte-dendritic cell-lineage. Mol. Immunol. 41, 1185–1198 (2004).
Article CAS Google Scholar
- Ramsey, C. et al. Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator. Eur. J. Immunol. 36, 305–317 (2006).
Article CAS Google Scholar
- Lee, J. W. et al. Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nature Immunol. 8, 181–190 (2007).
Article CAS Google Scholar
- Bottomley, M. J. et al. The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation. Nature Struct. Biol. 8, 626–633 (2001).
Article CAS Google Scholar
- Isaac, A., Wilcox, K. W. & Taylor, J. L. SP100B, a repressor of gene expression preferentially binds to DNA with unmethylated CpGs. J. Cell. Biochem. 98, 1106–1122 (2006).
Article CAS Google Scholar
- Bienz, M. The PHD finger, a nuclear protein-interaction domain. Trends Biochem. Sci. 31, 35–40 (2006).
Article CAS Google Scholar
- Akiyoshi, H. et al. Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. J. Biol. Chem. 279, 33984–33991 (2004).
Article CAS Google Scholar
- Pitkanen, J. et al. The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein. J. Biol. Chem. 275, 16802–16809 (2000).
Article CAS Google Scholar
- Pitkanen, J., Vahamurto, P., Krohn, K. & Peterson, P. Subcellular localization of the autoimmune regulator protein. J. Biol. Chem. 276, 19597–19602 (2001).
Article CAS Google Scholar
- Tao, Y. et al. AIRE recruits multiple transcriptional components to specific genomic regions through tethering to nuclear matrix. Mol. Immunol. 43, 335–345 (2006).
Article CAS Google Scholar
- Pitkanen, J. et al. Cooperative activation of transcription by autoimmune regulator AIRE and CBP. Biochem. Biophys. Res. Commun. 333, 944–953 (2005).
Article CAS Google Scholar
- Jacob, F., Perrin, D., Sanchez, C. & Monod, J. Operon: a group of genes with the expression coordinated by an operator. C. R. Hebd. Séances Acad. Sci. 250, 1727–1729 (1960).
CAS PubMed Google Scholar
- Purohit, S., Kumar, P. G., Laloraya, M. & She, J. X. Mapping DNA-binding domains of the autoimmune regulator protein. Biochem. Biophys. Res. Commun. 327, 939–944 (2005).
Article CAS Google Scholar
- Kumar, P. G. et al. The autoimmune regulator (AIRE) is a DNA-binding protein. J. Biol. Chem. 276, 41357–41364 (2001).
Article CAS Google Scholar
- Johnnidis, J. B. et al. Chromosomal clustering of genes controlled by the Aire transcription factor. Proc. Natl Acad. Sci. USA 102, 7233–7238 (2005).
Article CAS Google Scholar
- Uchida, D. et al. AIRE functions as an E3 ubiquitin ligase. J. Exp. Med. 199, 167–172 (2004).
Article CAS Google Scholar
- Bottomley, M. J. et al. NMR structure of the first PHD finger of autoimmune regulator protein (AIRE1). Insights into autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) disease. J. Biol. Chem. 280, 11505–11512 (2005).
Article CAS Google Scholar
- Pontynen, N. et al. Aire deficient mice do not develop the same profile of tissue-specific autoantibodies as APECED patients. J. Autoimmun. 27, 96–104 (2006).
Article Google Scholar
- Meager, A. et al. Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med. 3, e289 (2006).
Article Google Scholar
- Pugliese, A. et al. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nature Genet. 15, 293–297 (1997).
Article CAS Google Scholar
- Vafiadis, P. et al. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nature Genet. 15, 289–292 (1997).
Article CAS Google Scholar
- Aaltonen, J., Bjorses, P., Sandkuijl, L., Perheentupa, J. & Peltonen, L. An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21. Nature Genet. 8, 83–87 (1994).
Article CAS Google Scholar