Abstract

Autoimmune diseases, such as systemic lupus erythematosus (SLE), result from deficiencies in self-antigen tolerance processes, which require regulated dendritic cell (DC) function. In this study we evaluated the phenotype of DCs during the onset of SLE in a mouse model, in which deletion of the inhibitory receptor Fc?RIIb leads to the production of anti-nuclear antibodies and glomerulonephritis. Splenic DCs from Fc?RIIb-deficient mice suffering from SLE showed increased expression of co-stimulatory molecules. Furthermore, diseased mice showed an altered function of the nuclear factor-?B (NF-?B) transcription factor, which is involved in DC maturation. Compared with healthy animals, expression of the inhibitory molecule I?B-? was significantly decreased in mice suffering from SLE. Consistently, pharmacological inhibition of NF-?B activity in Fc?RIIb-deficient mice led to reduced susceptibility to SLE and prevented symptoms, such as anti-nuclear antibodies and kidney damage. Our data suggest that the occurrence of SLE is significantly influenced by alterations of NF-?B function, which can be considered as a new therapeutic target for this disease. © 2008 Blackwell Publishing Ltd.