Autoimmune regulator and self-tolerance - molecular and clinical aspects

Immunol Rev. 2016 May;271(1):127-40. doi: 10.1111/imr.12419.

Abstract

The establishment of central tolerance in the thymus is critical for avoiding deleterious autoimmune diseases. Autoimmune regulator (AIRE), the causative gene in autoimmune polyendocrine syndrome type-1 (APS-1), is crucial for the establishment of self-tolerance in the thymus by promoting promiscuous expression of a wide array of tissue-restricted self-antigens. This step is critical for elimination of high-affinity self-reactive T cells from the immunological repertoire, and for the induction of a specific subset of Foxp3(+) T-regulatory (Treg ) cells. In this review, we discuss the most recent advances in our understanding of how AIRE operates on molecular and cellular levels, as well as of how its loss of function results in breakdown of self-tolerance mechanisms characterized by a broad and heterogeneous repertoire of autoimmune phenotypes.

Keywords: T-regulatory cell; autoantibodies; autoimmune polyendocrine syndrome type-1; autoimmune regulator; autoimmunity; medullary thymic epithelial cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AIRE Protein
  • Animals
  • Autoantigens / immunology
  • Autoimmunity
  • Central Tolerance
  • Clonal Selection, Antigen-Mediated*
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Polyendocrinopathies, Autoimmune / genetics*
  • T-Lymphocytes, Regulatory / physiology*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Autoantigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Transcription Factors

Supplementary concepts

  • Autoimmune polyendocrinopathy syndrome, type 1