title: STAT4 deficiency reduces autoantibody production and glomerulonephritis in a mouse model of lupus.
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.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32601-0275, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xu
authors.forename: Biyan
authors.initials: B
authors.lastname: Duan
authors.forename: Byron P
authors.initials: BP
authors.lastname: Croker
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology*; D007668:Kidney / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D050797:STAT4 Transcription Factor / Q000172:deficiency* / Q000494:pharmacology; D050800:STAT6 Transcription Factor / Q000172:deficiency / Q000494:pharmacology
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor