title: Gene expression profiles for the human pancreas and purified islets in type 1 diabetes: new findings at clinical onset and in long-standing diabetes.
abstract: Type 1 diabetes (T1D) is caused by the selective destruction of the insulin-producing beta cells of the pancreas by an autoimmune response. Due to ethical and practical difficulties, the features of the destructive process are known from a small number of observations, and transcriptomic data are remarkably missing. Here we report whole genome transcript analysis validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and correlated with immunohistological observations for four T1D pancreases (collected 5 days, 9 months, 8 and 10 years after diagnosis) and for purified islets from two of them. Collectively, the expression profile of immune response and inflammatory genes confirmed the current views on the immunopathogenesis of diabetes and showed similarities with other autoimmune diseases; for example, an interferon signature was detected. The data also supported the concept that the autoimmune process is maintained and balanced partially by regeneration and regulatory pathway activation, e.g. non-classical class I human leucocyte antigen and leucocyte immunoglobulin-like receptor, subfamily B1 (LILRB1). Changes in gene expression in islets were confined mainly to endocrine and neural genes, some of which are T1D autoantigens. By contrast, these islets showed only a few overexpressed immune system genes, among which bioinformatic analysis pointed to chemokine (C-C motif) receptor 5 (CCR5) and chemokine (CXC motif) receptor 4) (CXCR4) chemokine pathway activation. Remarkably, the expression of genes of innate immunity, complement, chemokines, immunoglobulin and regeneration genes was maintained or even increased in the long-standing cases. Transcriptomic data favour the view that T1D is caused by a chronic inflammatory process with a strong participation of innate immunity that progresses in spite of the regulatory and regenerative mechanisms.
authors.affiliation: Laboratory of Immunobiology for Research and Applications to Diagnosis (LIRAD), Research Institute Germans Trias i Pujol, Badalona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Planas
authors.forename: J
authors.initials: J
authors.lastname: Carrillo
authors.forename: A
authors.initials: A
authors.lastname: Sanchez
authors.forename: M C Ruiz
authors.initials: MC
authors.lastname: de Villa
authors.forename: F
authors.initials: F
authors.lastname: Nuñez
authors.forename: J
authors.initials: J
authors.lastname: Verdaguer
authors.forename: R F L
authors.initials: RF
authors.lastname: James
authors.forename: R
authors.initials: R
authors.lastname: Pujol-Borrell
authors.forename: M
authors.initials: M
authors.lastname: Vives-Pi
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling; D050416:Glucagon-Secreting Cells / Q000378:metabolism; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology*; D000073718:Pancreatitis-Associated Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult; D000097625:HLA-E Antigens
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002097:C-Reactive Protein; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D000097625:HLA-E Antigens; C000612141:REG3A protein, human