Review

AIRE expands: new roles in immune tolerance and beyond

  • Nature Reviews Immunology volume 16, pages 247258 (2016)
  • doi:10.1038/nri.2016.9
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Abstract

More than 15 years ago, mutations in the autoimmune regulator (AIRE) gene were identified as the cause of autoimmune polyglandular syndrome type 1 (APS1). It is now clear that this transcription factor has a crucial role in promoting self-tolerance in the thymus by regulating the expression of a wide array of self-antigens that have the commonality of being tissue-restricted in their expression pattern in the periphery. In this Review, we highlight many of the recent advances in our understanding of the complex biology that is related to AIRE, with a particular focus on advances in genetics, molecular interactions and the effect of AIRE on thymic selection of regulatory T cells. Furthermore, we highlight new areas of biology that are potentially affected by this key regulator of immune tolerance.

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Acknowledgements

This work was supported by grants from the US National Institutes of Health to both M.S.A. and M.A.S.

Author information

Affiliations

  1. Diabetes Center, University of California, San Francisco, San Francisco, California 94143, USA.

    • Mark S. Anderson
  2. Departments of Pediatrics and of Microbiology/Immunology, School of Medicine, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

    • Maureen A. Su

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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Mark S. Anderson or Maureen A. Su.

Glossary

Autoimmune polyglandular syndrome type 1

(APS1). A rare human autoimmune disorder that is inherited in an autosomal recessive manner and is characterized by various endocrine deficiencies, chronic mucocutaneous candidiasis and ectodermal dystrophies. It is caused by mutations in the gene that encodes autoimmune regulator (AIRE).

Co-immunoprecipitation

A protein purification experiment used to identify proteins that are in complex with each other.

Yeast two-hybrid screening

A screening system for protein–protein interactions that results in the transcription of a reporter gene when a bait protein attached to a DNA-binding domain comes into contact with a prey protein bound to a transcriptional activator.

RNA interference

(RNAi). A phenomenon in which the expression of a gene is inhibited when a double-stranded complementary RNA is introduced into the organism.

Silenced chromatin states

Regions of chromatin that are in a repressed or silenced state, such that genes in these regions are not expressed.

Morisita–Horn similarity index

A statistical algorithm that is used to determine the similarity of complex sequences, such as those seen in individual T cell receptors.

Graft-versus-host disease

(GVHD). A potentially serious complication arising when donor-derived T cells attack host tissues, typically resulting in hepatic, dermatological and gastrointestinal damage. Acute GVHD occurs within the first 100 days after transplantation, whereas chronic GVHD occurs later and has a different pathophysiology.