Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID Mice

Abstract EN

Many studies have demonstrated that anti-dsDNA IgG is closely associated with lupus nephritis.

Recently, it was found that activation of the fibroblast growth factor-inducible 14 (Fn14) signaling pathway damages glomerular filtration barrier in MRL/lpr lupus-prone mice.

However, MRL/lpr mice have high titers of serum autoantibodies other than anti-dsDNA IgG.

The aim of this study was to further explore the effect of Fn14 deficiency on anti-dsDNA IgG-induced glomerular damage in severe combined immunodeficiency (SCID) mice that have no endogenous IgG.

Fn14 deficiency was generated in SCID mice.

The murine hybridoma cells producing control IgG or anti-dsDNA IgG were intraperitoneally injected into mice.

In two weeks, the urine, serum, and kidney tissue samples were harvested from mice at sacrifice.

It showed that the injection of anti-dsDNA IgG, but not control IgG hybridoma cells, induced proteinuria and glomerular damage in SCID mice.

Between the wild-type (WT) and knockout (KO) mice injected with anti-dsDNA IgG hybridoma cells, the latter showed a decrease in both proteinuria and glomerular IgG deposition.

The histopathological changes, inflammatory cell infiltration, and proinflammatory cytokine production were also attenuated in the kidneys of the Fn14-KO mice upon anti-dsDNA IgG injection.

Therefore, Fn14 deficiency effectively protects SCID mice from anti-dsDNA IgG-induced glomerular damage.