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

Mark S. Anderson, Emily S. Venanzi, Ludger Klein, Zhibin Chen, Stuart P. Berzins, Shannon J. Turley, Harald Von Boehmer, Roderick Bronson, Andrée Dierich, Christophe Benoist, Diane Mathis

Research output: Contribution to journalArticle

1629 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1395-1401
Number of pages7
JournalScience
Volume298
Issue number5597
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

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Autoimmunity
Thymus Gland
Autoimmune Diseases
Transcription Factors
Central Tolerance
Epithelial Cells
Antigens
Stromal Cells
Proteins
Genes
Ectopic Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Anderson, M. S., Venanzi, E. S., Klein, L., Chen, Z., Berzins, S. P., Turley, S. J., ... Mathis, D. (2002). Projection of an immunological self shadow within the thymus by the aire protein. Science, 298(5597), 1395-1401. https://doi.org/10.1126/science.1075958

Projection of an immunological self shadow within the thymus by the aire protein. / Anderson, Mark S.; Venanzi, Emily S.; Klein, Ludger; Chen, Zhibin; Berzins, Stuart P.; Turley, Shannon J.; Von Boehmer, Harald; Bronson, Roderick; Dierich, Andrée; Benoist, Christophe; Mathis, Diane.

In: Science, Vol. 298, No. 5597, 15.11.2002, p. 1395-1401.

Research output: Contribution to journalArticle

Anderson, MS, Venanzi, ES, Klein, L, Chen, Z, Berzins, SP, Turley, SJ, Von Boehmer, H, Bronson, R, Dierich, A, Benoist, C & Mathis, D 2002, 'Projection of an immunological self shadow within the thymus by the aire protein', Science, vol. 298, no. 5597, pp. 1395-1401. https://doi.org/10.1126/science.1075958
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 Nov 15;298(5597):1395-1401. https://doi.org/10.1126/science.1075958
Anderson, Mark S. ; Venanzi, Emily S. ; Klein, Ludger ; Chen, Zhibin ; Berzins, Stuart P. ; Turley, Shannon J. ; Von Boehmer, Harald ; Bronson, Roderick ; Dierich, Andrée ; Benoist, Christophe ; Mathis, Diane. / Projection of an immunological self shadow within the thymus by the aire protein. In: Science. 2002 ; Vol. 298, No. 5597. pp. 1395-1401.
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