Synonyms
Historical Background
One of the hallmarks of the adaptive immune system is its ability to distinguish between self and nonself, in order to be able to protect the individual from invading pathogens, while avoiding a potentially-destructive immune response against the body’s own tissues. Collectively known as immune tolerance, this ability is governed by an array of tightly regulated processes that are at the heart of immunological research. Much of our understanding of the mechanisms underlying immune tolerance has come from studying various cases of autoimmune disorders, which occur as a consequence of breakdown of self-tolerance mechanisms. Autoimmune polyglandular syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a monogenic autoimmune disorder characterized by devastating multiorgan pathological manifestations. In 1997, two research consortia cloned the gene...
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abramson J, Goldfarb Y. AIRE: from promiscuous molecular partnerships to promiscuous gene expression. Eur J Immunol. 2016;46:22–33. https://doi.org/10.1002/eji.201545792.
Abramson J, Husebye ES. Autoimmune regulator and self-tolerance – molecular and clinical aspects. Immunol Rev. 2016;271:127–40. https://doi.org/10.1111/imr.12419.
Abramson J, Giraud M, Benoist C, Mathis D. Aire’s partners in the molecular control of immunological tolerance. Cell. 2010;140:123–35. https://doi.org/10.1016/j.cell.2009.12.030.
Anderson MS, Su MA. AIRE expands: new roles in immune tolerance and beyond. Nat Rev Immunol. 2016;16:247–58. https://doi.org/10.1038/nri.2016.9.
Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002;298:1395–401. https://doi.org/10.1126/science.1075958.
Aschenbrenner K, D’Cruz LM, Vollmann EH, Hinterberger M, Emmerich J, Swee LK, et al. Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire + medullary thymic epithelial cells. Nat Immunol. 2007;8:351–8. https://doi.org/10.1038/ni1444.
Bjorses P, Pelto-Huikko M, Kaukonen J, Aaltonen J, Peltonen L, Ulmanen I. Localization of the APECED protein in distinct nuclear structures. Hum Mol Genet. 1999;8:259–66. https://doi.org/10.1093/Hmg/8.2.259.
Chuprin A, Avin A, Goldfarb Y, Herzig Y, Levi B, Jacob A, et al. The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance. Nat Immunol. 2015;16:737–45. https://doi.org/10.1038/ni.3194.
Finnish-German AC. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet. 1997;17:399–403. https://doi.org/10.1038/ng1297-399.
Fujikado N, Mann AO, Bansal K, Romito KR, Ferre EM, Rosenzweig SD, et al. Aire inhibits the generation of a perinatal population of interleukin-17A-producing gammadelta T cells to promote immunologic tolerance. Immunity. 2016;45:999–1012. https://doi.org/10.1016/j.immuni.2016.10.023.
Haljasorg U, Bichele R, Saare M, Guha M, Maslovskaja J, Kond K, et al. A highly conserved NF-kappaB-responsive enhancer is critical for thymic expression of Aire in mice. Eur J Immunol. 2015;45:3246–56. https://doi.org/10.1002/eji.201545928.
Heino M, Peterson P, Kudoh J, Nagamine K, Lagerstedt A, Ovod V, et al. Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem Biophys Res Commun. 1999;257:821–5. https://doi.org/10.1006/bbrc.1999.0308.
Herzig Y, Nevo S, Bornstein C, Brezis MR, Ben-Hur S, Shkedy A, et al. Transcriptional programs that control expression of the autoimmune regulator gene Aire. Nat Immunol. 2017;18. https://doi.org/10.1038/ni.3638.
Husebye ES, Perheentupa J, Rautemaa R, Kampe O. Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I. J Intern Med. 2009;265:514–29. https://doi.org/10.1111/j.1365-2796.2009.02090.x.
Kisand K, Boe Wolff AS, Podkrajsek KT, Tserel L, Link M, Kisand KV, et al. Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med. 2010;207:299–308. https://doi.org/10.1084/jem.20091669.
Koh AS, Kingston RE, Benoist C, Mathis D. Global relevance of Aire binding to hypomethylated lysine-4 of histone-3. Proc Natl Acad Sci USA. 2010;107:13016–21. https://doi.org/10.1073/pnas.1004436107.
Kumar PG, Laloraya M, Wang CY, Ruan QG, Davoodi-Semiromi A, Kao KJ, et al. The autoimmune regulator (AIRE) is a DNA-binding protein. J Biol Chem. 2001;276:41357–64. https://doi.org/10.1074/jbc.M104898200.
LaFlam TN, Seumois G, Miller CN, Lwin W, Fasano KJ, Waterfield M, et al. Identification of a novel cis-regulatory element essential for immune tolerance. J Exp Med. 2015;212:1993–2002. https://doi.org/10.1084/jem.20151069.
Lee HM, Bautista JL, Scott-Browne J, Mohan JF, Hsieh CS. A broad range of self-reactivity drives thymic regulatory T cell selection to limit responses to self. Immunity. 2012;37:475–86. https://doi.org/10.1016/j.immuni.2012.07.009.
Marx A, Hohenberger P, Hoffmann H, Pfannschmidt J, Schnabel P, Hofmann HS, et al. The autoimmune regulator AIRE in thymoma biology: autoimmunity and beyond. J Thorac Oncol. 2010;5:S266–72. https://doi.org/10.1097/JTO.0b013e3181f1f63f.
Mathis D, Benoist C. Aire. Annu Rev Immunol. 2009;27:287–312. https://doi.org/10.1146/annurev.immunol.25.022106.141532.
Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M, et al. Positional cloning of the APECED gene. Nat Genet. 1997;17:393–8. https://doi.org/10.1038/ng1297-393.
Oftedal BE, Hellesen A, Erichsen MM, Bratland E, Vardi A, Perheentupa J, et al. Dominant mutations in the autoimmune regulator AIRE are associated with common organ-specific autoimmune diseases. Immunity. 2015;42:1185–96. https://doi.org/10.1016/j.immuni.2015.04.021.
Perniola R, Musco G. The biophysical and biochemical properties of the autoimmune regulator (AIRE) protein. Biochim Biophys Acta. 2014;1842:326–37. https://doi.org/10.1016/j.bbadis.2013.11.020.
Perry JS, Lio CW, Kau AL, Nutsch K, Yang Z, Gordon JI, et al. Distinct contributions of Aire and antigen-presenting-cell subsets to the generation of self-tolerance in the thymus. Immunity. 2014;41:414–26. https://doi.org/10.1016/j.immuni.2014.08.007.
Pitkanen J, Doucas V, Sternsdorf T, Nakajima T, Aratani S, Jensen K, et al. The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein. J Biol Chem. 2000;275:16802–9. https://doi.org/10.1074/jbc.M908944199.
Puel A, Doffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, 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. 2010;207:291–7. https://doi.org/10.1084/jem.20091983.
Yanagihara T, Sanematsu F, Sato T, Uruno T, Duan X, Tomino T, et al. Intronic regulation of Aire expression by Jmjd6 for self-tolerance induction in the thymus. Nat Commun. 2015;6:8820. https://doi.org/10.1038/ncomms9820.
Yang S, Fujikado N, Kolodin D, Benoist C, Mathis D. Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance. Science. 2015;348:589–94. https://doi.org/10.1126/science.aaa7017.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Benhar, I., Abramson, J. (2018). AIRE. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101979
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101979
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences