Interferon-α initiates type 1 diabetes in nonobese diabetic mice
- 26 August 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (34), 12439-12444
- https://doi.org/10.1073/pnas.0806439105
Abstract
With the goal of identifying changes in gene expression in CD4(+) T cells during the development of diabetes in the nonobese diabetic (NOD) mouse, we used DNA microarrays to analyze gene expression in CD4(+) T cells from the pancreatic draining lymph nodes of NOD/BDC 2.5 T cell receptor transgenic and WT NOD mice at different ages. At 4 and 6 weeks of age, we found up-regulation of a number of genes that are known to be induced by IFN-alpha. IFN-alpha levels and IFN-alpha-producing plasmacytoid dendritic cells were increased in the PLNs of 3- to 4-week-old NOD mice. Moreover, blockade of IFN-alpha receptor 1 in NOD mice by a neutralizing antibody at 2-3 weeks of age significantly delayed the onset and decreased the incidence of type 1 diabetes, increased the relative number of immature dendritic cells in the PLNs, and enhanced the ability of spleen CD4(+) T cells to produce IL-4 and IL-10. These findings demonstrate that IFN-alpha in the PLNs is an essential initiator in the pathogenesis of type 1 diabetes in NOD mice.Keywords
This publication has 31 references indexed in Scilit:
- Toll-like Receptor 2 Senses β-Cell Death and Contributes to the Initiation of Autoimmune DiabetesImmunity, 2007
- TYPE I INTERFERONS (α/β) IN IMMUNITY AND AUTOIMMUNITYAnnual Review of Immunology, 2005
- THE NOD MOUSE: A Model of Immune DysregulationAnnual Review of Immunology, 2005
- Dendritic Cell Responses to Early Murine Cytomegalovirus InfectionThe Journal of Experimental Medicine, 2003
- Complete Suppression of Insulitis and Diabetes in NOD mice Lacking Interferon Regulatory Factor-1Journal of Autoimmunity, 2001
- Oral Use of Interferon-alpha Delays the Onset of Insulin-Dependent Diabetes Mellitus in Nonobese Diabetes MiceJournal of Interferon & Cytokine Research, 1999
- Islet expression of interferon-α precedes diabetes in both the BB rat and streptozotocin-treated miceImmunity, 1994
- Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process.The Journal of Experimental Medicine, 1994
- Onset of insulin-dependent diabetes mellitus after interferon-alfa therapy for hairy cell leukaemiaThe Lancet, 1994
- Following a diabetogenic T cell from genesis through pathogenesisCell, 1993