Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke.
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Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. / 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.
In: BLOOD, Vol. 120, No. 18, 18, 2012, p. 3793-3802.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke.
AU - Gelderblom, Mathias
AU - Weymar, Anna
AU - Bernreuther, Christian
AU - Velden, Joachim
AU - Arunachalam, Priyadharshini
AU - Steinbach, Karin
AU - Orthey, Ellen
AU - Arumugam, Thiruma V
AU - Leypoldt, Frank
AU - Simova, Olga
AU - Thom, Vivien
AU - Friese, Manuel A.
AU - Prinz, Immo
AU - Hölscher, Christoph
AU - Glatzel, Markus
AU - Korn, Thomas
AU - Gerloff, Christian
AU - Tolosa, Eva
AU - Magnus, Tim
PY - 2012
Y1 - 2012
N2 - 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 ?? and ?? T cells in a murine model of stroke and distinguished 2 different T cell-dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-? produced by CD4(+) T cells induced TNF-? production in macrophages, whereas IL-17A secreted by ?? T cells led to neutrophil recruitment. The synergistic effect of TNF-? 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.
AB - 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 ?? and ?? T cells in a murine model of stroke and distinguished 2 different T cell-dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-? produced by CD4(+) T cells induced TNF-? production in macrophages, whereas IL-17A secreted by ?? T cells led to neutrophil recruitment. The synergistic effect of TNF-? 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.
U2 - 10.1182/blood-2012-02-412726
DO - 10.1182/blood-2012-02-412726
M3 - SCORING: Journal article
VL - 120
SP - 3793
EP - 3802
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 18
M1 - 18
ER -
