title: Autoimmune Renal Disease Is Exacerbated by S1P-Receptor-1-Dependent Intestinal Th17 Cell Migration to the Kidney.
abstract: Th17 cells are most abundant in the gut, where their presence depends on the intestinal microbiota. Here, we examined whether intestinal Th17 cells contribute to extra-intestinal Th17 responses in autoimmune kidney disease. We found high frequencies of Th17 cells in the kidneys of patients with antineutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis. We utilized photoconversion of intestinal cells in Kaede mice to track intestinal T cell mobilization upon glomerulonephritis induction, and we found that Th17 cells egress from the gut in a S1P-receptor-1-dependent fashion and subsequently migrate to the kidney via the CCL20/CCR6 axis. Depletion of intestinal Th17 cells in germ-free and antibiotic-treated mice ameliorated renal disease, whereas expansion of these cells upon Citrobacter rodentium infection exacerbated pathology. Thus, in some autoimmune settings, intestinal Th17 cells migrate into target organs, where they contribute to pathology. Targeting the intestinal Th17 cell "reservoir" may present a therapeutic strategy for these autoimmune disorders.
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Krebs
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Krohn
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Koyro
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Silke R
authors.initials: SR
authors.lastname: Brix
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Riedel
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bartsch
authors.affiliation: Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wiech
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie, und Hygiene, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie, und Hygiene, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Fischer
authors.affiliation: Klinik für Allgemeinchirurgie, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Busch
authors.affiliation: Institut für Immunologie, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.affiliation: Philipps-Universität Marburg, Institut für Medizinische Mikrobiologie und Krankenhaushygiene, 35043 Marburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steinhoff
authors.affiliation: The Francis Crick Institute, Midland Road, London NW1 1AT, UK.
authors.forename: Brigitta
authors.initials: B
authors.lastname: Stockinger
authors.affiliation: I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Laura Garcia
authors.initials: LG
authors.lastname: Perez
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Ulrich O
authors.initials: UO
authors.lastname: Wenzel
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Janneck
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
authors.affiliation: Klinik für Allgemeinchirurgie, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gagliani
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Rolf A K
authors.initials: RAK
authors.lastname: Stahl
authors.affiliation: I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany. Electronic address: panzer@uke.de.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D044082:Citrobacter rodentium; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000276:immunology; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000276:immunology*; D006801:Humans; D007422:Intestines / Q000276:immunology; D007668:Kidney / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D049349:Receptors, Lysosphingolipid / Q000276:immunology*; D000081025:Sphingosine-1-Phosphate Receptors; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors