title: Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritis.
abstract: Mechanisms that initiate lupus nephritis and cause progression to end-stage renal disease remain poorly understood. In this study, we show that lupus-prone New Zealand Mixed 2410 mice that develop a severe glomerulosclerosis and rapidly progressive renal disease overexpress IL-4 in vivo. In these mice, STAT6 deficiency or anti-IL-4 Ab treatment decreases type 2 cytokine responses and ameliorates kidney disease, particularly glomerulosclerosis, despite the presence of high levels of IgG anti-dsDNA Abs. STAT4 deficiency, however, decreases type 1 and increases type 2 cytokine responses, and accelerates nephritis, in the absence of high levels of IgG anti-dsDNA Abs. Thus, STAT6 and IL-4 may selectively contribute to the development of glomerulosclerosis, whereas STAT4 may play a role in autoantibody production.
authors.affiliation: University of Cincinnati College of Medicine, Department of Internal Medicine, Veterans Affairs Medical Center and Children's Medical Center, Cincinnati, OH 45220, USA.
authors.forename: Ram Raj
authors.initials: RR
authors.lastname: Singh
authors.forename: Vijay
authors.initials: V
authors.lastname: Saxena
authors.forename: Song
authors.initials: S
authors.lastname: Zang
authors.forename: Lily
authors.initials: L
authors.lastname: Li
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: David P
authors.initials: DP
authors.lastname: Witte
authors.forename: Chaim O
authors.initials: CO
authors.lastname: Jacob
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4