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Blood, 1 August 2007, Vol. 110, No. 3, pp. 954-961. Prepublished online as a Blood First Edition Paper on May 4, 2007; DOI 10.1182/blood-2006-08-043786. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-043786v1 110/3/954    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Enzler, T. Articles by Dranoff, G. Search for Related Content PubMed PubMed Citation Articles by Enzler, T. Articles by Dranoff, G. Related Collections Hematopoiesis Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of ß cells Thomas Enzler1, Silke Gillessen1, Michael Dougan1, James P. Allison2, Donna Neuberg3, Darryl A. Oble4, Martin Mihm4, and Glenn Dranoff1 1 Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; 2 Howard Hughes Medical Institute and Program in Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY; 3 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; and 4 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA The pathogenesis of type 1 diabetes (T1D) involves the immune-mediated destruction of insulin-producing ß cells in the pancreatic islets of Langerhans. Genetic analysis of families with a high incidence of T1D and nonobese diabetic (NOD) mice, a prototypical model of the disorder, uncovered multiple susceptibility loci, although most of the underlying immune defects remain to be delineated. Here we report that aged mice doubly deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) manifest insulitis, destruction of insulin-producing ß cells, and compromised glucose homeostasis. Macrophages from mutant mice produce increased levels of p40 after LPS stimulation, whereas concurrent ablation of interferon- (IFN-) ameliorates the disease. The administration of antibodies that block cytotoxic T lymphocyte associated antigen-4 (CTLA-4) to young mutant mice precipitates the onset of insulitis and hyperglycemia. These results, together with previous reports of impaired hematopoietic responses to GM-CSF and IL-3 in patients with T1D and in NOD mice, indicate that functional deficiencies of these cytokines contribute to diabetes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Gaudreau, C. Guindi, M. Menard, G. Besin, G. Dupuis, and A. Amrani Granulocyte-Macrophage Colony-Stimulating Factor Prevents Diabetes Development in NOD Mice by Inducing Tolerogenic Dendritic Cells that Sustain the Suppressive Function of CD4+CD25+ Regulatory T Cells J. Immunol., September 15, 2007; 179(6): 3638 - 3647. [Abstract] [Full Text] [PDF]

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