Skip to main content
SpringerLink
Log in

AIRE

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

  • 94 Accesses

Synonyms

AIRE-1; APECED protein; Autoimmune regulator

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

Log in via an institution

Institutional subscriptions

References

  • Abramson J, Goldfarb Y. AIRE: from promiscuous molecular partnerships to promiscuous gene expression. Eur J Immunol. 2016;46:22–33. doi:10.1002/eji.201545792.

    Article  CAS  PubMed  Google Scholar 

  • Abramson J, Husebye ES. Autoimmune regulator and self-tolerance – molecular and clinical aspects. Immunol Rev. 2016;271:127–40. doi:10.1111/imr.12419.

    Article  CAS  PubMed  Google Scholar 

  • Abramson J, Giraud M, Benoist C, Mathis D. Aire’s partners in the molecular control of immunological tolerance. Cell. 2010;140:123–35. doi:10.1016/j.cell.2009.12.030.

    Article  CAS  PubMed  Google Scholar 

  • Anderson MS, Su MA. AIRE expands: new roles in immune tolerance and beyond. Nat Rev Immunol. 2016;16:247–58. doi:10.1038/nri.2016.9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1126/science.1075958.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1038/ni1444.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1093/Hmg/8.2.259.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1038/ni.3194.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1038/ng1297-399.

    Article  Google Scholar 

  • 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. doi:10.1016/j.immuni.2016.10.023.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1002/eji.201545928.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1006/bbrc.1999.0308.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1038/ni.3638.

    Google Scholar 

  • 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. doi:10.1111/j.1365-2796.2009.02090.x.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1084/jem.20091669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1073/pnas.1004436107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1074/jbc.M104898200.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1084/jem.20151069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1016/j.immuni.2012.07.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1097/JTO.0b013e3181f1f63f.

    Article  PubMed  Google Scholar 

  • Mathis D, Benoist C. Aire. Annu Rev Immunol. 2009;27:287–312. doi:10.1146/annurev.immunol.25.022106.141532.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1038/ng1297-393.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1016/j.immuni.2015.04.021.

    Article  CAS  PubMed  Google Scholar 

  • Perniola R, Musco G. The biophysical and biochemical properties of the autoimmune regulator (AIRE) protein. Biochim Biophys Acta. 2014;1842:326–37. doi:10.1016/j.bbadis.2013.11.020.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1016/j.immuni.2014.08.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1074/jbc.M908944199.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1084/jem.20091983.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1038/ncomms9820.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1126/science.aaa7017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

    Inbal Benhar & Jakub Abramson

  2. Present address: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA

    Inbal Benhar

Authors
  1. Inbal Benhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jakub Abramson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jakub Abramson .

Editor information

Editors and Affiliations

  1. Dept. Biological Science, Department of Molecular Science and Tech College of Natural Science, Suwon, Korea (Republic of)

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this entry

Cite this entry

Benhar, I., Abramson, J. (2017). AIRE. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101979-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101979-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-6438-9

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation