Blockade of IL-18 receptor signaling delays the onset of autoimmune disease in MRL-Faslpr mice.

Blockade of IL-18 Receptor Signaling Delays the Onset of Autoimmune Disease in MRL-Fas Mice

Costimulation by B7-1 and B7-2 is required for autoimmune disease in MRL-Faslpr mice.

Autoimmune lupus nephritis is dependent on infiltrating autoreactive leukocytes and Igs. B7 costimulatory molecules (B7-1 and B7-2) provide signals essential for T cell activation and Ig class switching. In MRL-Faslpr mice, a model of human lupus, although multiple tissues are targeted for autoimmune injury, nephritis is fatal. We identified intrarenal B7-1 and B7-2 expression, restricted to ki...

Inducible co-stimulator null MRL-Faslpr mice: uncoupling of autoantibodies and T cell responses in lupus.

MRL/MpJ-Tnfrsf6lpr (MRL-Faslpr) mice develop a spontaneous T cell-dependent autoimmune disease that shares features with human lupus, including fatal nephritis, systemic pathology, and autoantibodies (autoAb). The inducible co-stimulator (ICOS) is upregulated on activated T cells and modulates T cell-mediated responses. To investigate whether ICOS has an essential role in regulating autoimmune ...

Translational Nephrology RAS meets SLE ∗

The renin-angiotensin system (RAS) plays an important role in the pathogenesis of glomerular diseases. To delineate more precisely the role of RAS in creating renal injury, knockout mouse strains lacking the angiotensin type 1 or type 2 receptors (AT1 and AT2) have proven very informative. Hence, in their elegant study that was published in the April 2009 issue of the Journal of Clinical Invest...

A proinflammatory role of IL-18 in the development of spontaneous autoimmune disease.

Serum from patients with systemic lupus erythematosus (SLE) contained significantly higher concentrations of IL-18 than normal individuals. MRL/lpr mice, which develop spontaneous lupus-like autoimmune disease, also had higher serum levels of IL-18 than wild-type MRL/++ mice. Daily injections of IL-18 or IL-18 plus IL-12 resulted in accelerated proteinuria, glomerulonephritis, vasculitis, and r...