| First Author | Li Q | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 34 | Pages | 12439-44 |
| PubMed ID | 18716002 | Mgi Jnum | J:138932 |
| Mgi Id | MGI:3806882 | Doi | 10.1073/pnas.0806439105 |
| Citation | Li Q, et al. (2008) Interferon-alpha initiates type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A 105(34):12439-44 |
| abstractText | 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. |
