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

Genes Immun. 2006 Oct;7(7):555-67. doi: 10.1038/sj.gene.6364329. Epub 2006 Aug 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunoglobulin G / metabolism
  • Interferon-alpha / biosynthesis*
  • Interferon-beta / biosynthesis*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Nephritis / etiology
  • Lupus Nephritis / pathology
  • Mice
  • Poly I-C / pharmacology*
  • Proteinuria / etiology
  • Signal Transduction


  • Antibodies, Antinuclear
  • Immunoglobulin G
  • Interferon-alpha
  • Interferon-beta
  • Poly I-C