title: CXCL5 drives neutrophil recruitment in TH17-mediated GN.
abstract: Neutrophil trafficking to sites of inflammation is essential for the defense against bacterial and fungal infections, but also contributes to tissue damage in TH17-mediated autoimmunity. This process is regulated by chemokines, which often show an overlapping expression pattern and function in pathogen- and autoimmune-induced inflammatory reactions. Using a murine model of crescentic GN, we show that the pathogenic TH17/IL-17 immune response induces chemokine (C-X-C motif) ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive neutrophils that contribute to renal tissue injury. By contrast, CXCL5 was dispensable for neutrophil recruitment and effective bacterial clearance in a murine model of acute bacterial pyelonephritis. In line with these findings, CXCL5 expression was highly upregulated in the kidneys of patients with ANCA-associated crescentic GN as opposed to patients with acute bacterial pyelonephritis. Our data therefore identify CXCL5 as a potential therapeutic target for the restriction of pathogenic neutrophil infiltration in TH17-mediated autoimmune diseases while leaving intact the neutrophil function in protective immunity against invading pathogens.
authors.affiliation: III. Medical Clinic and.
authors.forename: Erik M
authors.initials: EM
authors.lastname: Disteldorf
authors.affiliation: III. Medical Clinic and.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Krebs
authors.affiliation: III. Medical Clinic and.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.affiliation: III. Medical Clinic and.
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany;
authors.forename: Geraldine
authors.initials: G
authors.lastname: Nouailles
authors.affiliation: Institute of Molecular Medicine and Experimental Immunology, Bonn, Germany;
authors.forename: André
authors.initials: A
authors.lastname: Tittel
authors.affiliation: III. Medical Clinic and.
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.affiliation: III. Medical Clinic and.
authors.forename: Gesa
authors.initials: G
authors.lastname: Stege
authors.affiliation: III. Medical Clinic and.
authors.forename: Silke
authors.initials: S
authors.lastname: Brix
authors.affiliation: Department of Nephropathology, Erlangen University Hospital, Erlangen, Germany; and.
authors.forename: Joachim
authors.initials: J
authors.lastname: Velden
authors.affiliation: Institutes of Pathology and.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wiech
authors.affiliation: Institutes of Pathology and.
authors.forename: Udo
authors.initials: U
authors.lastname: Helmchen
authors.affiliation: III. Medical Clinic and.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
authors.affiliation: III. Medical Clinic and.
authors.forename: Anett
authors.initials: A
authors.lastname: Peters
authors.affiliation: III. Medical Clinic and.
authors.forename: Sabrina B
authors.initials: SB
authors.lastname: Bennstein
authors.affiliation: III. Medical Clinic and.
authors.forename: Anna
authors.initials: A
authors.lastname: Kaffke
authors.affiliation: Institute of Molecular Medicine and Experimental Immunology, Bonn, Germany;
authors.forename: Chrystel
authors.initials: C
authors.lastname: Llanto
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
authors.affiliation: Immunology, Hamburg-Eppendorf University Hospital, Hamburg-Eppendorf, Germany;
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.affiliation: III. Medical Clinic and.
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.affiliation: Institute of Molecular Medicine and Experimental Immunology, Bonn, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany;
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: III. Medical Clinic and panzer@uke.uni-hamburg.de.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology*; D015854:Up-Regulation
chemical_list: D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018925:Chemokines; C475895:Cxcl1 protein, mouse; C094739:Cxcl5 protein, mouse; D020381:Interleukin-17
keywords: CXCL5; GN; IL-17; chemokines; immunology; neutrophils