Immune system STROKE Immune system Neutralization of the

Immune system STROKE Immune system Neutralization of the IL-17 axis diminishes neutrophil invasion ？ protects frombystander and Ischemic Stroke STROKE 11307120204 张昊澄 MPO is an abundant heme protein in neutrophils

MICE Wt Normal mice Rag 1 -/- mice deficient in recombination activating gene-1 Tcrd-/ mice devoid of γδT cell Il 17 ra-/- IL-17 receptor subunit A knockout mice Cxcr 2 -/ CXCR-1 receptor knockout mice MCAO：middle cerebral artery occlusion

Reduced Infarct size IFNγ CD 4+ αβT macrophage TNF-α stroke Neutralization astrocyte γδT IL-17 A neutrophils CXCL-1

The number of T cells increased dramatically

Reduced Infarct size IFNγ CD 4+ αβT macrophage TNF-α stroke Neutralization astrocyte γδT IL-17 A neutrophils CXCL-1

IL-17 A attracts neutrophils to the infarcted hemisphere

Reduced Infarct size IFNγ CD 4+ αβT macrophage TNF-α stroke Neutralization astrocyte γδT IL-17 A neutrophils CXCL-1

Recruitment of neutrophils——CXCL-1

Reduced Infarct size IFNγ CD 4+ αβT macrophage TNF-α stroke Neutralization astrocyte γδT IL-17 A neutrophils CXCL-1

Neutralization of IL-17 A is protective in stroke

mice autoptic brain tissue human IL-17 positive cell Target！

Reference： 1. Fonarow GC, Smith EE, Saver JL, et al. Timelines of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation. 2011; 123(7): 750 -758. 2. Vivien Thom, Manuel A. Friese, Immo Prinz, Christoph Hölscher, Markus Glatzel, Thomas Korn, Arunachalam, Karin Steinbach, Ellen Orthey, Thiruma V. Arumugam, Frank Leypoldt, Olga Simova, Mathias Gelderblom, Anna Weymar, Christian Bernreuther, Joachim Velden, Priyadharshini of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke 3. Reijerkerk A, Kooij G, van der Pol SM, et al. Tissue-type plasminogen activator is a regulator of monocyte diapedesis through the brain endothelial barrier. J Immunol. 2008; 181(5): 3563574. 4. Siao CJ, Fernandez SR, Tsirka SE. Cell typespecific roles for tissue plasminogen activator released by neurons or microglia after excitotoxic injury. J Neurosci. 2003; 23(8): 3234 -3242.