Global gene expression changes in type 1 diabetes: insights into autoimmune response in the target organ and in the periphery.
Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destruction of the insulin-producing β cells. Research into the pathogenesis of T1D has been hindered by the lack of detection of the autoimmune process during the asymptomatic period and by the inaccessibility to the target tissue. Therefore current understanding of the immunological phenomena that take place in the pancreas of the patients is very limited and much of the current knowledge on T1D has been obtained using animal models. Microarray technology and bioinformatics allow the comparison of the gene expression profile - transcriptome - in normal and pathological conditions, creating a global picture of altered processes. Microarray experiments have defined new transcriptional alterations associated with several autoimmune diseases, and are focused on the identification of specific biomarkers. In this review we summarize current data on gene expression profiles in T1D from an immunological point of view. Reported transcriptome studies have been performed in T1D patients and Non-Obese Diabetic mouse models analyzing peripheral blood, lymphoid organs and pancreas/islets. In the periphery, the distinctive profiles are inflammatory pathways inducible by IL-1β and IFNs that can help in the identification of new biomarkers. In the target organ, a remarkable finding is the overexpression of inflammatory and innate immune response genes and the active autoimmune response at longstanding stages, contrary to the pre-existing concept of acute autoimmune process in T1D.
Planas
Raquel
R
Laboratory of Immunobiology for Research and Applications to Diagnosis (LIRAD), Blood and Tissue Bank, Research Institute Germans Trias i Pujol, Badalona, Spain.
Pujol-Borrell
Ricardo
R
Vives-Pi
Marta
M
D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation; D050417:Insulin-Secreting Cells / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD
D015415:Biomarkers