Interferon-alpha initiates type 1 diabetes in nonobese diabetic mice.
Proc Natl Acad Sci U S A
; 105(34): 12439-44, 2008 Aug 26.
Article
in En
| MEDLINE
| ID: mdl-18716002
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interferon-alpha
/
Diabetes Mellitus, Type 1
/
Receptor, Interferon alpha-beta
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2008
Type:
Article
Affiliation country:
United States