Interferon regulatory factor-1 gene deletion decreases glomerulonephritis in MRL/lpr mice

✍ Scribed by Christopher M. Reilly; Selen Olgun; David Goodwin; Robert M. Gogal Jr.; Arben Santo; Jason W. Romesburg; S. Ansar Ahmed; Gary S. Gilkeson

• Book ID: 102162067
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 487 KB
• Volume: 36
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200535245

✦ Synopsis

Abstract

To investigate the role of interferon regulatory factor‐1 (IRF‐1) in the development of lupus nephritis, IRF‐1^–/–^ genotype mice were bred onto the MRL/lpJfas^lpr^ (MRL/lpr) background. We examined kidney mesangial cell function and disease progression. Endpoints evaluated included inflammatory mediators, autoantibody production, immune complex deposition, renal pathology, T cell subset analysis, and duration of survival. Mesangial cells cultured from IRF‐1^–/–^ mice produced significantly lower levels of nitric oxide and IL‐12 but not TNF‐α when stimulated with LPS + IFN‐γ. IRF‐1^–/–^ mice showed less aggravated dermatitis compared to the wild‐type mice. Anti‐double‐stranded DNA production and proteinuria were significantly decreased in IRF‐1^–/–^ mice compared to IRF‐1^+/+^ mice. IgG and C3 deposition as well as glomerulonephritis were decreased in IRF‐1^–/–^ mice at 26 wk of age compared to the IRF‐1^+/+^ mice. Splenic CD4^–^CD8^–^CD44^+^ T cells were decreased while CD4^+^CD25^+^ T cells were increased in the IRF‐1^–/–^ mice when compared to IRF‐1^+/+^ mice. Survival rates (ED~50~) were 22 wk for IRF‐1^+/+^ mice and 45 wk for IRF‐1^–/–^ mice. These findings suggest an important role of IRF‐1 in mediating renal disease in MRL/lpr mice.