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, Prinz, Immo, Holscher, Christoph, Glatzel, Markus, Korn, Thomas, Gerloff, Christian, Tolosa, Eva and Magnus, Tim (2012) Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. Blood, 120 18: 3793-3802. doi:10.1182/blood-2012-02-412726


Author 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
Prinz, Immo
Holscher, Christoph
Glatzel, Markus
Korn, Thomas
Gerloff, Christian
Tolosa, Eva
Magnus, Tim
Title Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2012-09-13
Sub-type Article (original research)
DOI 10.1182/blood-2012-02-412726
Volume 120
Issue 18
Start page 3793
End page 3802
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2013
Language eng
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 two different T cell-dependent proinflammatory pathways in ischemiareperfusion injury. IFN-γ produced by CD4+ T cells induced TNF-α production in macrophages, while 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 three hours after stroke induction decreased infarct size and improved neurological outcome in the murine model. In autoptic brain tissue of stroke patients, 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Prepublished online: 13 September 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
 
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Created: Fri, 14 Sep 2012, 10:09:06 EST by Dr Thiruma V Arumugam on behalf of School of Biomedical Sciences