Scientific Article
previous document  unige:11367  next document
add to browser collection

Genetic susceptibility to polyI:C-induced IFNalpha/beta-dependent accelerated disease in lupus-prone mice

Jorgensen, T. N.
Thurman, J.
Falta, M. T.
Metzger, T. E.
Flannery, S. A.
Kappler, Johne
Marrack, Pilippa
show hidden authors show all authors [1 - 9]
Published in Genes and immunity. 2006, vol. 7, no. 7, p. 555-567
Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology. Associations between viral infections and the onset of SLE have been suggested, and recent studies have provided evidence that type I interferons (IFNalpha/beta) might play a role in the SLE disease process. Viruses and interferons have also been implicated in mouse models of SLE. We generated a model of accelerated proteinuria, in which lupus-prone mice were injected repeatedly with polyinosinic:polycytidylic acid (polyI:C), mimicking exposure to virus-derived double stranded RNA (dsRNA), leading to the production of IFNalpha/beta. PolyI:C-treated (B6.Nba2 x NZW)F1 and (B6 x NZW)F1 hybrid mice developed significantly increased levels of anti-dsDNA autoantibodies, characteristic of lupus. Most significantly, polyI:C-treated (B6.Nba2 x NZW)F1 mice, but not (B6 x NZW)F1 or parental strains, developed lupus-like nephritis in an accelerated fashion, which was dependent on IFNalpha/beta and associated with elevated deposition of total IgG, IgG2a and complement factor C3 in the glomerular capillary walls. These data suggest that reagents, which increase the levels of endogenous IFNalpha/beta (directly or indirectly), can accelerate the course of lupus-like nephritis, the development of which is dependent on the presence of both NZW- and Nba2-encoded genes.
Keywords AnimalsAntibodies, Antinuclear/bloodDisease Models, AnimalFemaleGenetic Predisposition to DiseaseHumansImmunoglobulin G/metabolismInterferon-alpha/*biosynthesisInterferon-beta/*biosynthesisKidney Glomerulus/drug effects/immunology/pathologyLupus Erythematosus, Systemic/*genetics/*immunologyLupus Nephritis/etiology/pathologyMicePoly I-C/*pharmacologyProteinuria/etiologySignal Transduction
PMID: 16900204
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version:
(ISO format)
JORGENSEN, T. N. et al. Genetic susceptibility to polyI:C-induced IFNalpha/beta-dependent accelerated disease in lupus-prone mice. In: Genes and immunity, 2006, vol. 7, n° 7, p. 555-567. doi: 10.1038/sj.gene.6364329

443 hits

0 download


Deposited on : 2010-08-27

Export document
Format :
Citation style :