title: IL-17F Promotes Tissue Injury in Autoimmune Kidney Diseases.
abstract: The TH17 immune response has a central role in the pathogenesis of autoimmune diseases, implicating the TH17 master cytokine, IL-17A, as the critical mediator of diseases such as human and experimental crescentic GN. However, the relative importance of additional TH17 effector cytokines, including IL-17F, in immune-mediated tissue injury remains to be fully elucidated. Here, using a mouse model of acute crescentic GN (nephrotoxic nephritis), we identified CD4+T cells and γδ T cells as the major cellular source of IL-17F in the inflamed kidney. Interventional studies using IL-17F gene-deficient mice, IL-17F-neutralizing antibodies, and adoptive transfer experiments into Rag1-/-mice demonstrated that CD4+T cell-derived IL-17F drives renal tissue injury in acute crescentic GN. Notably, IL-17F-deficient nephritic mice had fewer renal infiltrating neutrophils than wild-type nephritic mice, and neutrophil depletion did not affect the course of GN in IL-17F-deficient mice. Moreover, in the chronic model of pristane-induced SLE, IL-17F-deficient mice developed less severe disease than wild-type mice, with respect to survival and renal injury. Finally, we show that IL-17F induced expression of the neutrophil-attracting chemokines CXCL1 and CXCL5 in kidney cells. The finding that IL-17F has a nonredundant function in the development of renal tissue injury in experimental GN might be of great importance for the development of anti-IL-17 cytokine therapies in TH17-mediated human autoimmune diseases.
authors.affiliation: III. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Riedel
authors.affiliation: III. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.affiliation: III. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Krohn
authors.affiliation: III. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.affiliation: III. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Malte A
authors.initials: MA
authors.lastname: Kluger
authors.affiliation: III. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
authors.affiliation: III. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Krebs
authors.affiliation: III. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.affiliation: III. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany panzer@uke.uni-hamburg.de.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000473:pathology; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D020381:Interleukin-17 / Q000502:physiology*; D008297:Male; D051379:Mice; D009504:Neutrophils
chemical_list: D020381:Interleukin-17
keywords: cytokines; glomerulonephritis; immunology; lymphocytes; systemic lupus erythematosus