title: Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke.
abstract: The devastating effect of ischemic stroke is attenuated in mice lacking conventional and unconventional T cells, suggesting that inflammation enhances tissue damage in cerebral ischemia. We explored the functional role of αβ and γδ T cells in a murine model of stroke and distinguished 2 different T cell-dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-γ produced by CD4(+) T cells induced TNF-α production in macrophages, whereas IL-17A secreted by γδ T cells led to neutrophil recruitment. The synergistic effect of TNF-α and IL-17A on astrocytes resulted in enhanced secretion of CXCL-1, a neutrophil chemoattractant. Application of an IL-17A-blocking antibody within 3 hours after stroke induction decreased infarct size and improved neurologic outcome in the murine model. In autoptic brain tissue of patients who had a stroke, we detected IL-17A-positive lymphocytes, suggesting that this aspect of the inflammatory cascade is also relevant in the human brain. We propose that selective targeting of IL-17A signaling might provide a new therapeutic option for the treatment of stroke.
authors.affiliation: Department of Neurology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Gelderblom
authors.forename: Anna
authors.initials: A
authors.lastname: Weymar
authors.forename: Christian
authors.initials: C
authors.lastname: Bernreuther
authors.forename: Joachim
authors.initials: J
authors.lastname: Velden
authors.forename: Priyadharshini
authors.initials: P
authors.lastname: Arunachalam
authors.forename: Karin
authors.initials: K
authors.lastname: Steinbach
authors.forename: Ellen
authors.initials: E
authors.lastname: Orthey
authors.forename: Thiruma V
authors.initials: TV
authors.lastname: Arumugam
authors.forename: Frank
authors.initials: F
authors.lastname: Leypoldt
authors.forename: Olga
authors.initials: O
authors.lastname: Simova
authors.forename: Vivien
authors.initials: V
authors.lastname: Thom
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Friese
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.forename: Thomas
authors.initials: T
authors.lastname: Korn
authors.forename: Christian
authors.initials: C
authors.lastname: Gerloff
authors.forename: Eva
authors.initials: E
authors.lastname: Tolosa
authors.forename: Tim
authors.initials: T
authors.lastname: Magnus
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D020521:Stroke / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17