期刊
BLOOD
卷 120, 期 18, 页码 3793-3802出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-02-412726
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资金
- Landesexzellen-zinitiative Hamburg
- ERANET/NANOSTROKE
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)
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