Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke Academic Article uri icon

abstract

  • 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

  • Gelderblom, Mathias
  • Weymar, Anna
  • Bernreuther, Christian
  • Velden, Joachim
  • Arunachalam, Priyadharshini
  • Steinbach, Karin
  • Orthey, Ellen
  • Arumugam, Thiruma V
  • Leypoldt, Frank
  • Simova, Olga
  • Thom, Vivien
  • Friese, Manuel A
  • Prinz, Immo
  • Hölscher, Christoph
  • Glatzel, Markus
  • Korn, Thomas
  • Gerloff, Christian
  • Tolosa, Eva
  • Magnus, Tim

publication date

  • November 1, 2012

published in