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

Zhiwei Xu, Biyan Duan, Byron P. Croker, Laurence Morel

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)189-198
Number of pages10
JournalClinical Immunology
Volume120
Issue number2
DOIs
StatePublished - Aug 2006
Externally publishedYes

Keywords

  • Autoantibodies
  • Cytokines
  • Glomerulonephritis
  • IL-12
  • IL-4
  • Lupus
  • Mouse models

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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