Early events in islets and pancreatic lymph nodes in autoimmune diabetes.
The specific contributions of islet cell microenvironment during the development of autoimmune type 1 diabetes remain unclear. The aims of this study were to identify early immune-driven abnormalities in islets and pancreatic lymph nodes of NOD mice by cDNA arrays. We compared gene expression profiles of purified islets and pancreatic lymph nodes of 4-week-old NOD mice to NOD-SCID and BALB/c mice. To further characterize the networks implicated in beta-cell destruction, we also performed a time-course analysis using islets and pancreatic lymph nodes of NOD mice from 2 to 25 weeks of age. We found consistent changes by cDNA arrays and RT-PCR analyses among islet genes before the detection of CD3+ T cells in the islet periphery associated with dendritic cell attraction, lymphocyte homing, and apoptosis. In contrast to IL-1, TYNFSF13B and osteopontin genes which were specifically activated, the immunoregulatory cytokine IL-11 was poorly detected in NOD islets and pancreatic lymph nodes. Genes involved in angiogenesis were also specifically activated in NOD islets of 2 and 4 weeks of age. The present time-course macroarray and RT-PCR analyses provides a detailed picture of the different genes involved in autoimmune diabetes and illustrates the importance of islet cell microenvironment that prepares the late beta-cell destruction.
Aspord
Caroline
C
INSERM 449, Mécanismes moléculaires du diabète, Faculté de médecine Laennec, rue Guillaume Parradin, 69008 Lyon, France.
Rome
Sophie
S
Thivolet
Charles
C
D000367:Age Factors; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction