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  • Review Article
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The role of AIRE in human autoimmune disease

Nature Reviews Endocrinology volume 7, pages 25–33 (2011)Cite this article

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Abstract

The autoimmune regulator (AIRE) gene encodes a transcription factor involved in the presentation of tissue-restricted antigens during T-cell development in the thymus. Mutations of this gene lead to type 1 autoimmune polyglandular syndrome (APS-1), also termed autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is characterized by the clinical presentation of at least two of a triad of underlying disorders: Addison disease, hypoparathyroidism and chronic mucocutaneous candidiasis. This Review describes the process of positive and negative selection of developing T cells in the thymus and the role of AIRE as a regulator of peripheral antigen presentation. Furthermore, it addresses how mutations of this gene lead to the failure to eliminate autoreactive T cells, which can lead to clinical autoimmune syndromes.

Key Points

  • More than 60 mutations of the autoimmune regulator (AIRE) gene are associated with the development of type 1 autoimmune polyglandular syndrome (APS-1) or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome

  • AIRE plays an important part in shaping the T-cell repertoire through its role in negative selection of autoreactive T cells

  • In addition, mutations of AIRE can directly, by affecting the deletion of autoreactive T cells in the thymus, and indirectly, by promoting anti-interferon antibodies, affect other aspects of immune responses

  • The clinical manifestations associated with APS-1 classically involve mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency, but can vary in scope and timing

  • Production of autoantibodies against cytokines, including interferon α, interleukin 17A and interleukin 22, in patients with APS-1 may be responsible for the development of mucocutaneous candidiasis

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Figure 1: Potential mechanisms of AIRE deficiency.

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References

  1. Bubanovic, I. V. Crossroads of extrathymic lymphocytes maturation pathways. Med. Hypotheses 61, 235–239 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Pantelouris, E. M. Absence of thymus in a mouse mutant. Nature 217, 370–371 (1968).

    Article  CAS  PubMed  Google Scholar 

  3. Cunliffe, V. T., Furley, A. J. & Keenan, D. Complete rescue of the nude mutant phenotype by a wild-type Foxn1 transgene. Mamm. Genome 13, 245–252 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Lind, E. F., Prockop, S. E., Porritt, H. E. & Petrie, H. T. Mapping precursor movement through the postnatal thymus reveals specific microenvironments supporting defined stages of early lymphoid development. J. Exp. Med. 194, 127–134 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pearse, M. et al. A murine early thymocyte developmental sequence is marked by transient expression of the interleukin 2 receptor. Proc. Natl Acad. Sci. USA 86, 1614–1618 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shinkai, Y. et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68, 855–867 (1992).

    Article  CAS  PubMed  Google Scholar 

  7. Jameson, S. C., Hogquist, K. A. & Bevan, M. J. Positive selection of thymocytes. Annu. Rev. Immunol. 13, 93–126 (1995).

    Article  CAS  PubMed  Google Scholar 

  8. Kisielow, P., Teh, H. S., Blüthmann, H. & von Boehmer, H. Positive selection of antigen-specific T cells in thymus by restricting MHC molecules. Nature 335, 730–733 (1988).

    Article  CAS  PubMed  Google Scholar 

  9. Scollay, R. G., Butcher, E. C. & Weissman, I. L. Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur. J. Immunol. 10, 210–218 (1980).

    Article  CAS  PubMed  Google Scholar 

  10. Klein, L., Hinterberger, M., Wirnsberger, G. & Kyewski, B. Antigen presentation in the thymus for positive selection and central tolerance induction. Nat. Rev. Immunol. 9, 833–844 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Silva-Santos, B., Pennington, D. J. & Hayday, A. C. Lymphotoxin-mediated regulation of gammadelta cell differentiation by alphabeta T cell progenitors. Science 307, 925–928 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Chin, R. K. et al. Lymphotoxin pathway directs thymic Aire expression. Nat. Immunol. 4, 1121–1127 (2003).

    Article  PubMed  Google Scholar 

  13. Martins, V. C., Boehm, T. & Bleul, C. C. Ltβr signaling does not regulate Aire-dependent transcripts in medullary thymic epithelial cells. J. Immunol. 181, 400–407 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Venanzi, E. S., Melamed, R., Mathis, D. & Benoist, C. The variable immunological self: genetic variation and nongenetic noise in Aire-regulated transcription. Proc. Natl Acad. Sci. USA 105, 15860–15865 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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  PubMed  PubMed Central  Google Scholar 

  16. 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  PubMed  Google Scholar 

  17. Abramson, J., Giraud, M., Benoist, C. & Mathis, D. Aire's partners in the molecular control of immunological tolerance. Cell 140, 123–135 (2010).

    Article  CAS  PubMed  Google Scholar 

  18. Guerau-de-Arellano, M., Mathis, D. & Benoist, C. Transcriptional impact of Aire varies with cell type. Proc. Natl Acad. Sci. USA 105, 14011–14016 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ferguson, B. J. et al. AIRE's CARD revealed, a new structure for central tolerance provokes transcriptional plasticity. J. Biol. Chem. 283, 1723–1731 (2008).

    Article  CAS  PubMed  Google Scholar 

  20. Mathis, D. & Benoist, C. A decade of AIRE. Nat. Rev. Immunol. 7, 645–650 (2007).

    Article  CAS  PubMed  Google Scholar 

  21. Jordan, M. S. et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2, 301–306 (2001).

    Article  CAS  PubMed  Google Scholar 

  22. 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  PubMed  Google Scholar 

  23. Kogawa, K. et al. Expression of AIRE gene in peripheral monocyte/dendritic cell lineage. Immunol. Lett. 80, 195–198 (2002).

    Article  CAS  PubMed  Google Scholar 

  24. Su, M. A. et al. Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire. J. Clin. Invest. 118, 1712–1726 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lee, J. W. et al. Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat. Immunol. 8, 181–190 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Gardner, J. M. et al. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science 321, 843-7 (2008).

  27. Poliani, P. L. et al. Human peripheral lymphoid tissues contain autoimmune regulator-expressing dendritic cells. Am. J. Pathol. 176, 1104–1112 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ikegami, H. Animal models of autoimmune polyglandular syndrome. Endocrinol. Metab. Clin. North Am. 31, 431–439 (2002).

    Article  PubMed  Google Scholar 

  29. 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  PubMed  Google Scholar 

  30. Gotter, J. & Kyewski, B. Regulating self-tolerance by deregulating gene expression. Curr. Opin. Immunol. 16, 741–745 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. 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  PubMed  PubMed Central  Google Scholar 

  32. 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  PubMed  PubMed Central  Google Scholar 

  33. Fan, Y. et al. Thymus-specific deletion of insulin induces autoimmune diabetes. EMBO J. 28, 2812–2824 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Babaya, N. et al. A new model of insulin-deficient diabetes: male NOD mice with a single copy of Ins1 and no Ins2. Diabetologia 49, 1222–1228 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Jaeckel, E., Lipes, M. A. & von Boehmer, H. Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes. Nat. Immunol. 5, 1028–1035 (2004).

    Article  CAS  PubMed  Google Scholar 

  36. 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  PubMed  Google Scholar 

  37. 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  PubMed  PubMed Central  Google Scholar 

  38. Björses, P. et al. Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. Am. J. Hum. Genet. 66, 378–392 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Wolff, A. S. et al. Autoimmune polyendocrine syndrome type 1 in Norway: phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene. J. Clin. Endocrinol. Metab. 92, 595–603 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Piirilä, H., Väliaho, J. & Vihinen, M. Immunodeficiency mutation databases (IDbases). Hum. Mutat. 27, 1200–1208 (2006), [online] (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Ahonen, P. Autoimmune polyendocrinopathy-candidosis--ectodermal dystrophy (APECED): autosomal recessive inheritance. Clin. Genet. 27, 535–542 (1985).

    Article  CAS  PubMed  Google Scholar 

  42. Zlotogora, J. & Shapiro, M. S. Polyglandular autoimmune syndrome type I among Iranian Jews. J. Med. Genet. 29, 824–826 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Aaltonen, J., Björses, P., Sandkuijl, L., Perheentupa, J. & Peltonen, L. An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21. Nat. Genet. 8, 83–87 (1994).

    Article  CAS  PubMed  Google Scholar 

  44. Björses, P. et al. Genetic homogeneity of autoimmune polyglandular disease type I. Am. J. Hum. Genet. 59, 879–886 (1996).

    PubMed  PubMed Central  Google Scholar 

  45. Aaltonen, J. et al. High-resolution physical and transcriptional mapping of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3 by FISH. Genome Res. 7, 820–829 (1997).

    Article  CAS  PubMed  Google Scholar 

  46. Kudoh, J. et al. Localization of 16 exons to a 450-kb region involved in the autoimmune polyglandular disease type I (APECED) on human chromosome 21q22.3. DNA Res. 4, 45–52 (1997).

    Article  CAS  PubMed  Google Scholar 

  47. Nagamine, K. et al. Positional cloning of the APECED gene. Nat. Genet. 17, 393–398 (1997).

    Article  CAS  PubMed  Google Scholar 

  48. Vogel, A. et al. Autoimmune regulator AIRE: evidence for genetic differences between autoimmune hepatitis and hepatitis as part of the autoimmune polyglandular syndrome type 1. Hepatology 33, 1047–1052 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Peterson, P., Pitkänen, J., Sillanpää, N. & Krohn, K. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a model disease to study molecular aspects of endocrine autoimmunity. Clin. Exp. Immunol. 135, 348–357 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Pearce, S. H. et al. A common and recurrent 13-bp deletion in the autoimmune regulator gene in British kindreds with autoimmune polyendocrinopathy type 1. Am. J. Hum. Genet. 63, 1675–1684 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Heino, M. et al. Mutation analyses of North American APS-1 patients. Hum. Mutat. 13, 69–74 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. [No authors listed] An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat. Genet. 17, 399–403 (1997).

  53. Cervato, S. et al. Evaluation of the autoimmune regulator (AIRE) gene mutations in a cohort of Italian patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) and in their relatives. Clin. Endocrinol. (Oxf.) 70, 421–428 (2009).

    Article  Google Scholar 

  54. Cihakova, D. et al. Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED. Hum. Mutat. 18, 225–232 (2001).

    Article  CAS  PubMed  Google Scholar 

  55. Heino, M. et al. APECED mutations in the autoimmune regulator (AIRE) gene. Hum. Mutat. 18, 205–211 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Husebye, E. S., Perheentupa, J., Rautemaa, R. & Kämpe, O. Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I. J. Intern. Med. 265, 514–529 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Podkrajsek, K. T. et al. Detection of a complete autoimmune regulator gene deletion and two additional novel mutations in a cohort of patients with atypical phenotypic variants of autoimmune polyglandular syndrome type 1. Eur. J. Endocrinol. 159, 633–639 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Buzi, F. et al. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome: time to review diagnostic criteria? J. Clin. Endocrinol. Metab. 88, 3146–3148 (2003).

    Article  CAS  PubMed  Google Scholar 

  59. Blizzard, R. M. & Kyle, M. Studies of the adrenal antigens and antibodies in Addison's disease. J. Clin. Invest. 42, 1653–1660 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hung, W., Migeon, C. J. & Parrott, R. H. A possible autoimmune basis for Addison's disease in three siblings, one with idiopathic hypoparathyroidism, pernicious anemia and superficial moniliasis. N. Engl. J. Med. 269, 658–663 (1963).

    Article  CAS  PubMed  Google Scholar 

  61. Kogut, M. D. & Brinegar, C. H. Jr. Addison's disease and diabetes mellitus. J. Pediatr. 81, 307–311 (1972).

    Article  CAS  PubMed  Google Scholar 

  62. Alimohammadi, M. et al. Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen. N. Engl. J. Med. 358, 1018–1028 (2008).

    Article  CAS  PubMed  Google Scholar 

  63. Meager, A. et al. Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med. 3, e289 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kisand, K. et al. Interferon autoantibodies associated with AIRE deficiency decrease the expression of IFN-stimulated genes. Blood 112, 2657–2666 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Puel, A. et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J. Exp. Med. 207, 291–297 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kisand, K. et al. Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J. Exp. Med. 207, 299–308 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Littman, D. R. & Rudensky, A. Y. Th17 and regulatory T cells in mediating and restraining inflammation. Cell 140, 845–858 (2010).

    Article  CAS  PubMed  Google Scholar 

  68. Rautemaa, R., Hietanen, J., Niissalo, S., Pirinen, S. & Perheentupa, J. Oral and oesophageal squamous cell carcinoma—a complication or component of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I). Oral Oncol. 43, 607–613 (2007).

    Article  PubMed  Google Scholar 

  69. Ward, L. et al. Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy. J. Clin. Endocrinol. Metab. 84, 844–852 (1999).

    CAS  PubMed  Google Scholar 

  70. Padeh, S., Theodor, R., Jonas, A. & Passwell, J. H. Severe malabsorption in autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome successfully treated with immunosuppression. Arch. Dis. Child. 76, 532–534 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dhodapkar, M. V., Lust, J. A. & Phyliky, R. L. T-cell large granular lymphocytic leukemia and pure red cell aplasia in a patient with type I autoimmune polyendocrinopathy: response to immunosuppressive therapy. Mayo Clin. Proc. 69, 1085–1088 (1994).

    Article  CAS  PubMed  Google Scholar 

  72. Ulinski, T. et al. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome with renal failure: impact of posttransplant immunosuppression on disease activity. J. Clin. Endocrinol. Metab. 91, 192–195 (2006).

    Article  CAS  PubMed  Google Scholar 

  73. Ströbel, P. et al. Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS-1). J. Pathol. 211, 563–571 (2007).

    Article  CAS  PubMed  Google Scholar 

  74. Evoli, A. et al. Thymoma in patients with MG: characteristics and long-term outcome. Neurology 59, 1844–1850 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Cetani, F. et al. A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis. J. Clin. Endocrinol. Metab. 86, 4747–4752 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Björses, P., Aaltonen, J., Horelli-Kuitunen, N., Yaspo, M. L. & Peltonen, L. Gene defect behind APECED: a new clue to autoimmunity. Hum. Mol. Genet. 7, 1547–1553 (1998).

    Article  PubMed  Google Scholar 

  77. Thornton, A. M. et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433–3441 (2010).

    Article  CAS  PubMed  Google Scholar 

  78. Ryan, K. R. et al. CD4+CD25+ T-regulatory cells are decreased in patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. J. Allergy Clin. Immunol. 116, 1158–1159 (2005).

    Article  CAS  PubMed  Google Scholar 

  79. Kekäläinen, E. et al. A defect of regulatory T cells in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J. Immunol. 178, 1208–1215 (2007).

    Article  PubMed  Google Scholar 

  80. Liston, A., Lesage, S., Wilson, J., Peltonen, L. & Goodnow, C. C. Aire regulates negative selection of organ-specific T cells. Nat. Immunol. 4, 350–354 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Liston, A. et al. Differentiation of regulatory Foxp3+ T cells in the thymic cortex. Proc. Natl Acad. Sci. USA 105, 11903–11908 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Aschenbrenner, K. et al. Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nat. Immunol. 8, 351–358 (2007).

    Article  CAS  PubMed  Google Scholar 

  83. Gebre-Medhin, G. et al. Cytochrome P450IA2 and aromatic L-amino acid decarboxylase are hepatic autoantigens in autoimmune polyendocrine syndrome type I. FEBS Lett. 412, 439–445 (1997).

    Article  CAS  PubMed  Google Scholar 

  84. Tuomi, T. et al. Antibodies to glutamic acid decarboxylase and insulin-dependent diabetes in patients with autoimmune polyendocrine syndrome type I. J. Clin. Endocrinol. Metab. 81, 1488–1494 (1996).

    CAS  PubMed  Google Scholar 

  85. Söderbergh, A. et al. Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I. J. Clin. Endocrinol. Metab. 89, 557–562 (2004).

    Article  CAS  PubMed  Google Scholar 

  86. Ekwall, O. et al. Identification of tryptophan hydroxylase as an intestinal autoantigen. Lancet 352, 279–283 (1998).

    Article  CAS  PubMed  Google Scholar 

  87. Krohn, K., Uibo, R., Aavik, E., Peterson, P. & Savilahti, K. Identification by molecular cloning of an autoantigen associated with Addison's disease as steroid 17 alpha-hydroxylase. Lancet 339, 770–773 (1992).

    Article  CAS  PubMed  Google Scholar 

  88. Hubert, F. X. et al. Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype. J. Immunol. 182, 3902–3918 (2009).

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Immunobiology and the School of Public Health, Yale University School of Medicine, 10 Amistad Street, 131D, New Haven, 06520, CT, USA

    Eitan M. Akirav, Nancy H. Ruddle & Kevan C. Herold

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E. M. Akirav and K. C. Herold researched the data for the article. All authors provided a substantial contribution to discussions of the content. E. M. Akirav and K. C. Herold wrote the article, and all authors reviewed and/or edited the manuscript before submission.

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Akirav, E., Ruddle, N. & Herold, K. The role of AIRE in human autoimmune disease. Nat Rev Endocrinol 7, 25–33 (2011). https://doi.org/10.1038/nrendo.2010.200

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