title: TH1 and TH17 cells promote crescent formation in experimental autoimmune glomerulonephritis.
abstract: Autoimmunity against the Goodpasture antigen α3IV-NC1 results in crescentic glomerulonephritis (GN). Both antibodies and T cells directed against α3IV-NC1 have been implicated in disease development and progression. Using the model of experimental autoimmune glomerulonephritis (EAG) in DBA/1 mice, we aimed to characterize the frequency and function of α3IV-NC1-specific CD4(+) T cells in the kidneys. DBA/1 mice repeatedly immunized with human α3IV-NC1 developed necrotizing/crescentic GN. Kidneys with crescentic GN contained CD4(+) cells responding to α3IV-NC1 with the production of IFN-γ or IL-17A, demonstrating the accumulation of both α3IV-NC1-specific TH1 and TH17 cells. To test the functional relevance of TH1 and TH17 cells, EAG was induced in DBA/1 mice deficient in IFN-γR, IL-17A or IL-23p19. Mice of all knockout groups mounted α3IV-NC1 IgG, developed nephrotic range proteinuria, and IgG deposition to the glomerular basement membranes at levels similar to immunized wild-type mice. However, all knockout groups showed significantly fewer glomerular crescents and attenuated tubulointerstitial damage. Our results suggest that both α3IV-NC1-specific TH1 and TH17 cells accumulate in the kidneys and are crucial for the development of necrotizing/crescentic GN.
authors.affiliation: Institute for Immunology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hünemörder
authors.affiliation: Institute for Immunology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Treder
authors.affiliation: Institute for Immunology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ahrens
authors.affiliation: Institute for Immunology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Valéa
authors.initials: V
authors.lastname: Schumacher
authors.affiliation: 3rd Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.affiliation: Institute for Pathology, University Hospital Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Menter
authors.affiliation: Laboratory of Immunobiology, Rega Institute, University of Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthys
authors.affiliation: Institute for Immunology, University Hospital Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
authors.affiliation: 3rd Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.affiliation: 3rd Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.affiliation: Institute for Pathology, University Hospital Basel, Switzerland.
authors.forename: Helmut
authors.initials: H
authors.lastname: Hopfer
authors.affiliation: Institute for Immunology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015551:Autoimmunity; D024141:Collagen Type IV / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D007668:Kidney / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011507:Proteinuria / Q000276:immunology / Q000378:metabolism; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D001324:Autoantigens; D024141:Collagen Type IV; D007074:Immunoglobulin G; D007371:Interferon-gamma; D020381:Interleukin-17; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D000096743:Interferon gamma Receptor; C098680:Il17a protein, mouse; C528688:interleukin-23 receptor, mouse; C057112:type IV collagen alpha3 chain
keywords: Goodpasture's syndrome; anti-GBM disease; immunology and pathology; lymphocytes; renal injury