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Nat Immunol. 2014 Mar;15(3):258-65. doi: 10.1038/ni.2820. Epub 2014 Jan 26.

The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.

Author information

1
1] Diabetes Center, University of California San Francisco, San Francisco, California, USA. [2] Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.
2
Diabetes Center, University of California San Francisco, San Francisco, California, USA.
3
Department of Microbiology & Immunology, University of California San Francisco, San Francisco, California, USA.
4
Department of Liver Sciences, Division of Transplantation Immunology & Mucosal Biology, Institute of Liver Studies, King's College London, London, UK.
5
Department of Medicine, University of California San Francisco, San Francisco, California, USA.
6
Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
7
1] Diabetes Center, University of California San Francisco, San Francisco, California, USA. [2] Department of Medicine, University of California San Francisco, San Francisco, California, USA.

Erratum in

  • Nat Immunol. 2014 Sep;15(9):894.

Abstract

The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activity of the transcriptional regulator Aire; however, the molecular mechanisms Aire uses to target loci encoding TSAs are unknown. Here we identified two Aire-interacting proteins known to be involved in gene repression, ATF7ip and MBD1, that were required for Aire's targeting of loci encoding TSAs. Moreover, Mbd1(-/-) mice developed pathological autoimmunity and had a defect in Aire-dependent thymic expression of genes encoding TSAs, which underscores the importance of Aire's interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance.

PMID:
24464130
PMCID:
PMC4172453
DOI:
10.1038/ni.2820
[Indexed for MEDLINE]
Free PMC Article
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