Modulation of nuclear factor-kappaB activity can influence the susceptibility to systemic lupus erythematosus

Immunology. 2009 Sep;128(1 Suppl):e306-14. doi: 10.1111/j.1365-2567.2008.02964.x. Epub 2008 Nov 7.


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 FcgammaRIIb leads to the production of anti-nuclear antibodies and glomerulonephritis. Splenic DCs from FcgammaRIIb-deficient mice suffering from SLE showed increased expression of co-stimulatory molecules. Furthermore, diseased mice showed an altered function of the nuclear factor-kappaB (NF-kappaB) transcription factor, which is involved in DC maturation. Compared with healthy animals, expression of the inhibitory molecule IkappaB-alpha was significantly decreased in mice suffering from SLE. Consistently, pharmacological inhibition of NF-kappaB activity in FcgammaRIIb-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-kappaB function, which can be considered as a new therapeutic target for this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Diterpenes / administration & dosage
  • Diterpenes / pharmacology
  • Female
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / metabolism
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • I-kappa B Proteins / agonists
  • I-kappa B Proteins / immunology
  • I-kappa B Proteins / metabolism
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / immunology*
  • NF-kappa B / metabolism
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology*
  • Receptors, IgG / metabolism
  • Rosiglitazone
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / pharmacology


  • Anti-Inflammatory Agents
  • Diterpenes
  • Fcgr2b protein, mouse
  • Hypoglycemic Agents
  • I-kappa B Proteins
  • NF-kappa B
  • Receptors, IgG
  • Thiazolidinediones
  • Rosiglitazone
  • andrographolide