Insulin alleles and autoimmune regulator (AIRE) gene expression both influence insulin expression in the thymus

J Autoimmun. 2005 Dec;25(4):312-8. doi: 10.1016/j.jaut.2005.08.006. Epub 2005 Oct 24.

Abstract

It is well established that the polymorphisms at the 5' of the insulin gene (IDDM2) confers susceptibility to type 1 diabetes, probably by modifying the level of insulin expression in the thymus that in turn influences immunological tolerance to insulin as self-antigen. AIRE is a transcription regulator which controls the expression of many peripheral antigens within the thymus, among them insulin. Results presented here confirm that insulin gene copies from both parental chromosomes are expressed in human thymus and that IDDM2 class III protective alleles are indeed associated with a higher level of insulin message expression. However, differences in insulin mRNA expression among different thymi were far wider than those determined by the class I and class III insulin gene alleles and maintained a clear correlation with AIRE expression. These results confirm the effect of IDDM2 alleles on insulin expression in the thymus, but suggest that the levels of AIRE may exert a stronger influence than IDDM2 alleles themselves.

Publication types

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

MeSH terms

  • Adult
  • Alleles*
  • Child
  • Child, Preschool
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / metabolism
  • Gene Dosage / immunology
  • Gene Expression Regulation / immunology*
  • Humans
  • Infant
  • Infant, Newborn
  • Insulin / biosynthesis*
  • Insulin / genetics*
  • Insulin / physiology
  • RNA, Messenger / biosynthesis
  • Thymus Gland / immunology
  • Thymus Gland / metabolism*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics*
  • Transcription Factors / physiology

Substances

  • APECED protein
  • Insulin
  • RNA, Messenger
  • Transcription Factors