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Upregulation of Lymphoid and Renal Interferon-γ mRNA in Autoimmune MRL-Fas lpr Mice with Lupus Nephritis

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MRL-Fas lpr mice develop an aggressive form of autoimmunity, characterized by immune complex-mediated glomerulonephritis and massive expansion of lymphoid tissues. Increased MHC class II expression by macrophages and renal parenchymal cells is a prominent feature of MRL-Fas lpr mice. Since interferon-γ (IFN-γ) is the major and the most potent inducer of MHC class II molecules it could play a pathogenic role in the disease process in MRL-Fas lpr. We have analyzed IFN-γ expression in normal and nephritic MRL-Fas lpr mice by examining renal and lymphoid IFN-γ-specific mRNA production, using reverse transcription—polymerase chain reaction (RT-PCR) and Northern blotting. We detect abundant IFN-γ mRNA expression in the kidney of nephritic MRL-Fas lpr by RT-PCR, whereas normal mice display absent or only very weak expression of this cytokine. By RT-PCR, IFN-γ mRNA is detectable in normal spleen, but is overexpressed in the enlarged spleen and lymph nodes of MRL-Fas lpr. Northern blotting using total RNA from tissues confirms abundant IFN-γ expression in spleen and lymph node of MRL-Fas lpr. We conclude that enhanced renal IFN-γ mRNA expression is a prominent feature of MRL-Fas lpr lupus nephritis. Increased IFN-γ produced by infiltrating T cells could lead to increased MHC class II expression by renal parenchymal cells, thereby promoting the nephritic process by augmentation of antigen presentation in the kidney of autoimmune MRL-Fas lpr.

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Fan, X., Wüthrich, R.P. Upregulation of Lymphoid and Renal Interferon-γ mRNA in Autoimmune MRL-Fas lpr Mice with Lupus Nephritis. Inflammation 21, 105–112 (1997). https://doi.org/10.1023/A:1027399027170

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