Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke

被引：389

作者：

Gelderblom, Mathias ^{[1
]}

Weymar, Anna ^{[1
]}

Bernreuther, Christian ^{[2
]}

Velden, Joachim ^{[3
]}

Arunachalam, Priyadharshini ^{[1
]}

Steinbach, Karin ^{[4
]}

Orthey, Ellen ^{[1
]}

Arumugam, Thiruma V. ^{[5
]}

Leypoldt, Frank ^{[1
]}

Simova, Olga ^{[1
]}

Thom, Vivien ^{[6
]}

Friese, Manuel A. ^{[4
]}

Prinz, Immo ^{[7
]}

Hoelscher, Christoph ^{[8
]}

Glatzel, Markus ^{[2
]}

Korn, Thomas ^{[9
]}

Gerloff, Christian ^{[1
]}

Tolosa, Eva ^{[6
]}

Magnus, Tim ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, D-20246 Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Inst Neuropathol, D-20246 Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Inst Pathol, D-20246 Hamburg, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Ctr Mol Neurobiol, Res Grp Neuroimmunol, D-20246 Hamburg, Germany

[5] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia

[6] Univ Med Ctr Hamburg Eppendorf, Inst Immunol, D-20246 Hamburg, Germany

[7] Hannover Med Sch, Inst Immunol, D-3000 Hannover, Germany

[8] Res Ctr Borstel, Borstel, Germany

[9] Tech Univ Munich, Dept Neurol, Munich, Germany

来源：

BLOOD | 2012年 / 120卷 / 18期

关键词：

T-CELLS; PLASMINOGEN-ACTIVATOR; INTERFERON-GAMMA; CXC CHEMOKINE; BRAIN; INJURY; INHIBITION; NEURONS; MICE; EXPRESSION;

D O I：

10.1182/blood-2012-02-412726

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 alpha beta and gamma delta T cells in a murine model of stroke and distinguished 2 different T cell-dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-gamma produced by CD4(+) T cells induced TNF-alpha production in macrophages, whereas IL-17A secreted by gamma delta T cells led to neutrophil recruitment. The synergistic effect of TNF-alpha 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. (Blood.2012;120(18):3793-3802)

引用

页码：3793 / 3802

页数：10

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