• Mathias Gelderblom, Anna Weymar, Christian Bernreuther, Joachim Velden, Priyadharshini Arunachalam, Karin Steinbach, Ellen Orthey, Thiruma V Arumugam, Frank Leypoldt, Olga Simova, Vivien Thom, Manuel A Friese, Immo Prinz, Christoph Hölscher, Markus Glatzel, Thomas Korn, Christian Gerloff, Eva Tolosa, and Tim Magnus.
• Department of Neurology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
• Blood. 2012 Nov 1;120(18):3793-802.

AbstractThe 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.

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