title: FMS-like tyrosine kinase 3 ligand treatment does not ameliorate experimental rapidly progressive glomerulonephritis.
abstract: Fms-like tyrosine kinase 3-ligand (FL) is a growth factor that may expand dendritic cell and regulatory T cell populations. We hypothesised that FL-induced regulatory T cells would protect mice from experimental rapidly progressive glomerulonephritis. To determine if FL was able to enhance regulatory T cell populations, C57BL/6 mice received 10 days of daily intraperitoneal injections of either FL or phosphate buffered saline. To induce accelerated autologous-phase anti-mouse glomerular basement membrane glomerulonephritis, mice were sensitized to sheep globulin 4 days prior to the induction of glomerulonephritis with sheep anti-mouse glomerular basement membrane globulin, and experiments ended 10 days later. FL was administered before, throughout and during the sensitization phase of this glomerulonephritis model. Renal disease and systemic immunity to the nephritogenic antigen were assessed. FL increased regulatory T cell and plasmacytoid dendritic cell proportions within spleen and lymph nodes. FL administration prior to glomerulonephritis did not protect mice from renal injury. When FL was given throughout the model, FL treated mice had reduced survival, with more interstitial neutrophils and glomerular CD11c+ cells than controls. Systemic immune responses showed increased IL-17A production from splenocytes, with more CD11c+ cells, but reduced plasmacytoid dendritic cell proportions in spleen and lymph nodes, despite increased regulatory T cell proportions. Under homeostatic conditions, FL expanded regulatory T cell and plasmacytoid dendritic cell populations, but FL enhanced systemic inflammatory responses and conventional dendritic cell populations when given during experimental glomerulonephritis, suggesting selective attempts to suppress pathogenic immunity by dendritic cell manipulation may be harmful.
authors: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; Department of Nephrology, Monash Health, Clayton, Victoria, Australia.
authors: Joanna R
authors: JR
authors: Ghali
authors: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia.
authors: Kim M
authors: KM
authors: O'Sullivan
authors: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia.
authors: Peter J
authors: PJ
authors: Eggenhuizen
authors: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; Department of Nephrology, Monash Health, Clayton, Victoria, Australia.
authors: Stephen R
authors: SR
authors: Holdsworth
authors: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; Department of Nephrology, Monash Health, Clayton, Victoria, Australia; Department of Paediatric Nephrology, Monash Health, Clayton, Victoria, Australia.
authors: A Richard
authors: AR
authors: Kitching
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005916:Globulins / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012756:Sheep; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D051941:fms-Like Tyrosine Kinase 3 / Q000276:immunology
chemical_list: D005916:Globulins; D020381:Interleukin-17; D008565:Membrane Proteins; C084881:flt3 ligand protein; D007371:Interferon-gamma; D051941:fms-Like Tyrosine Kinase 3