Interferon-α initiates type 1 diabetes in nonobese diabetic mice

Qing Li, Baohui Xu, Sara A. Michie, Kathleen H. Rubins, Robert D. Schreriber, Hugh O. McDevitt

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

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-α. IFN-α levels and IFN-α-producing plasmacytoid dendritic cells were increased in the PLNs of 3- to 4-week-old NOD mice. Moreover, blockade of IFN-α 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-α in the PLNs is an essential initiator in the pathogenesis of type 1 diabetes in NOD mice.

Original languageEnglish
Pages (from-to)12439-12444
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number34
DOIs
StatePublished - Aug 26 2008

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