Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke
| Autor: | Tim Magnus, Anna Weymar, Joachim Velden, Olga Simova, Thiruma V. Arumugam, Manuel A. Friese, Christian Bernreuther, Immo Prinz, Mathias Gelderblom, Markus Glatzel, Ellen Orthey, Christian Gerloff, Priyadharshini Arunachalam, Christoph Hölscher, Vivien Thom, Thomas Korn, Frank Leypoldt, Eva Tolosa, Karin Steinbach |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Neutrophils
T-Lymphocytes Immunology Ischemia Enzyme-Linked Immunosorbent Assay Mice Transgenic Inflammation Real-Time Polymerase Chain Reaction Biochemistry Brain Ischemia Proinflammatory cytokine Brain ischemia Mice Animals Humans Medicine Stroke business.industry Interleukin-17 Cell Biology Hematology Human brain Flow Cytometry medicine.disease Immunohistochemistry Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Neutrophil Infiltration Interleukin 17 Signal transduction medicine.symptom business Signal Transduction |
| Zdroj: | Blood. 120:3793-3802 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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 2 different T cell–dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-γ produced by CD4+ T cells induced TNF-α production in macrophages, whereas 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 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|