| First Author | Gelderblom M | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 18 | Pages | 3793-802 |
| PubMed ID | 22976954 | Mgi Jnum | J:191283 |
| Mgi Id | MGI:5461406 | Doi | 10.1182/blood-2012-02-412726 |
| Citation | Gelderblom M, et al. (2012) Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. Blood 120(18):3793-802 |
| abstractText | 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 alphabeta and gammadelta 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 gammadelta 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. |
