STAT4 deficiency reduces autoantibody production and glomerulonephritis in a mouse model of lupus

Clin Immunol. 2006 Aug;120(2):189-98. doi: 10.1016/j.clim.2006.03.009. Epub 2006 May 19.

Abstract

To determine the respective role of the IL-12 and IL-4 pathways in the pathogenesis of systemic lupus erythematosus, we bred the Stat4 and Stat6 null alleles onto the lupus-prone mouse B6.TC, which is a congenic derivative of NZM2410. This model is characterized by abnormal splenocyte expansion, distribution and architecture, T cell activation, peripheral B cell development, production of anti-nuclear antibodies, and proliferative glomerulonephritis. STAT4 deficiency normalized the expression of each of these disease markers toward or to C57BL/6 levels. In contrast, STAT6 deficiency impacted splenocyte expansion and architecture, T cell activation, and anti-nuclear autoantibody production, but without any significant effect on B cell development or renal pathology. These results show that the IL-12/STAT4 pathway is involved in multiple disease-associated phenotypes in the B6.TC mouse. In contrast, the IL-4/STAT6 pathway regulates only a subset of disease markers that did not affect renal pathology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis*
  • Autoantibodies / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • Cytokines / biosynthesis
  • Disease Models, Animal*
  • Female
  • Glomerulonephritis / immunology*
  • Kidney / pathology
  • Lymphocyte Subsets / immunology*
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • STAT4 Transcription Factor / deficiency*
  • STAT4 Transcription Factor / pharmacology
  • STAT6 Transcription Factor / deficiency
  • STAT6 Transcription Factor / pharmacology

Substances

  • Autoantibodies
  • Cytokines
  • STAT4 Transcription Factor
  • STAT6 Transcription Factor