Projection of an immunological self shadow within the thymus by the aire protein - PubMed (original) (raw)

. 2002 Nov 15;298(5597):1395-401.

doi: 10.1126/science.1075958. Epub 2002 Oct 10.

Affiliations

• PMID: 12376594
• DOI: 10.1126/science.1075958

Projection of an immunological self shadow within the thymus by the aire protein

Mark S Anderson et al. Science. 2002.

Abstract

Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used aire- deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue- restricted antigens in medullary epithelial cells of the thymus. This hypothesis proved correct. The mutant animals exhibited a defined profile of autoimmune diseases that depended on the absence of aire in stromal cells of the thymus. Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens. These findings highlight the importance of thymically imposed "central" tolerance in controlling autoimmunity.

PubMed Disclaimer

Comment in

• Immunology. Exposing thy self.
  Ohashi PS. Ohashi PS. Science. 2002 Nov 15;298(5597):1348-9. doi: 10.1126/science.1079323. Science. 2002. PMID: 12434042 No abstract available.

Similar articles

• Immunology. Exposing thy self.
  Ohashi PS. Ohashi PS. Science. 2002 Nov 15;298(5597):1348-9. doi: 10.1126/science.1079323. Science. 2002. PMID: 12434042 No abstract available.
• Disruption of immunological tolerance: role of AIRE gene in autoimmunity.
  Rizzi M, Ferrera F, Filaci G, Indiveri F. Rizzi M, et al. Autoimmun Rev. 2006 Feb;5(2):145-7. doi: 10.1016/j.autrev.2005.09.001. Epub 2005 Sep 13. Autoimmun Rev. 2006. PMID: 16431348 Review.
• Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self.
  Derbinski J, Schulte A, Kyewski B, Klein L. Derbinski J, et al. Nat Immunol. 2001 Nov;2(11):1032-9. doi: 10.1038/ni723. Nat Immunol. 2001. PMID: 11600886
• Autoimmune regulator controls T cell help for pathogenetic autoantibody production in collagen-induced arthritis.
  Campbell IK, Kinkel SA, Drake SF, van Nieuwenhuijze A, Hubert FX, Tarlinton DM, Heath WR, Scott HS, Wicks IP. Campbell IK, et al. Arthritis Rheum. 2009 Jun;60(6):1683-93. doi: 10.1002/art.24501. Arthritis Rheum. 2009. PMID: 19479827
• Recent insights into the role and molecular mechanisms of the autoimmune regulator (AIRE) gene in autoimmunity.
  Fierabracci A. Fierabracci A. Autoimmun Rev. 2011 Jan;10(3):137-43. doi: 10.1016/j.autrev.2010.08.019. Epub 2010 Sep 17. Autoimmun Rev. 2011. PMID: 20850570 Review.

Cited by

• Antigen recognition by autoreactive CD4⁺ thymocytes drives homeostasis of the thymic medulla.
  Irla M, Guerri L, Guenot J, Sergé A, Lantz O, Liston A, Imhof BA, Palmer E, Reith W. Irla M, et al. PLoS One. 2012;7(12):e52591. doi: 10.1371/journal.pone.0052591. Epub 2012 Dec 27. PLoS One. 2012. PMID: 23300712 Free PMC article.
• Revelations in Thymic Epithelial Cell Biology and Heterogeneity from Single-Cell RNA Sequencing and Lineage Tracing Methodologies.
  Morales-Sanchez A, Shissler SC, Cowan JE, Bhandoola A. Morales-Sanchez A, et al. Methods Mol Biol. 2023;2580:25-49. doi: 10.1007/978-1-0716-2740-2_2. Methods Mol Biol. 2023. PMID: 36374449 Free PMC article.
• Mesenchymal stromal cells in the thymus.
  Nitta T. Nitta T. Inflamm Regen. 2022 Nov 2;42(1):33. doi: 10.1186/s41232-022-00219-5. Inflamm Regen. 2022. PMID: 36320070 Free PMC article. Review.
• Human autoantibodies neutralizing type I IFNs: From 1981 to 2023.
  Bastard P, Gervais A, Le Voyer T, Philippot Q, Cobat A, Rosain J, Jouanguy E, Abel L, Zhang SY, Zhang Q, Puel A, Casanova JL. Bastard P, et al. Immunol Rev. 2024 Mar;322(1):98-112. doi: 10.1111/imr.13304. Epub 2024 Jan 9. Immunol Rev. 2024. PMID: 38193358 Review.
• The role of gut microbiota in immune homeostasis and autoimmunity.
  Wu HJ, Wu E. Wu HJ, et al. Gut Microbes. 2012 Jan-Feb;3(1):4-14. doi: 10.4161/gmic.19320. Epub 2012 Jan 1. Gut Microbes. 2012. PMID: 22356853 Free PMC article. Review.

Publication types

MeSH terms

Substances

Grants and funding

• 2 P30 DK36836-16/DK/NIDDK NIH HHS/United States
• 2T32 DK07260-26/DK/NIDDK NIH HHS/United States
• KO8-DK59958-01A1/DK/NIDDK NIH HHS/United States
• R01 DK60027-01/DK/NIDDK NIH HHS/United States
• T32CA70083-05/CA/NCI NIH HHS/United States

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Ovid Technologies, Inc.

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)
  • NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases

• Research Materials

  • Jackson Laboratory JAX®Mice Database