TY - JOUR
T1 - Interferon-α initiates type 1 diabetes in nonobese diabetic mice
AU - Li, Qing
AU - Xu, Baohui
AU - Michie, Sara A.
AU - Rubins, Kathleen H.
AU - Schreriber, Robert D.
AU - McDevitt, Hugh O.
PY - 2008/8/26
Y1 - 2008/8/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=50449087345&partnerID=8YFLogxK
U2 - 10.1073/pnas.0806439105
DO - 10.1073/pnas.0806439105
M3 - Article
C2 - 18716002
AN - SCOPUS:50449087345
SN - 0027-8424
VL - 105
SP - 12439
EP - 12444
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 34
ER -