title: Insulin alleles and autoimmune regulator (AIRE) gene expression both influence insulin expression in the thymus.
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.
authors.affiliation: Laboratory of Immunology for Research Applied to Diagnosis (LIRAD), Blood and Tissue Bank, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol, Crtra. del Canyet s/n, 08916 Badalona, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Sabater
authors.forename: Xavier
authors.initials: X
authors.lastname: Ferrer-Francesch
authors.forename: Mireia
authors.initials: M
authors.lastname: Sospedra
authors.forename: Pepi
authors.initials: P
authors.lastname: Caro
authors.forename: Manel
authors.initials: M
authors.lastname: Juan
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pujol-Borrell
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D018628:Gene Dosage / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D000096927:AIRE Protein
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D014157:Transcription Factors; D000096927:AIRE Protein