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

Lidia Sabater, Xavier Ferrer-Francesch, Mireia Sospedra, Pepi Caro, Manel Juan, Ricardo Pujol-Borrell

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37 Citations (Scopus)

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. © 2005 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)312-318
JournalJournal of Autoimmunity
Volume25
DOIs
Publication statusPublished - 1 Dec 2005

Keywords

  • Autoimmunity
  • Insulin
  • Thymus
  • Tolerance
  • Type 1 diabetes

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