Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke
Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke
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DOI：
10.1182/blood-2012-02-412726
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发表时间：
2012-11-01
期刊：
影响因子：
20.3
通讯作者：
Magnus, Tim
中科院分区：
文献类型：
--
作者：
Gelderblom, Mathias;Weymar, Anna;Magnus, Tim
在缺乏常规和非常规T细胞的小鼠中，缺血性中风的破坏性影响被减弱，这表明炎症增强了脑缺血中的组织损伤。我们探讨了α-β和γ-增量T细胞在卒中小鼠模型中的功能作用，并区分了两种不同的T细胞依赖的促炎途径在脑缺血-再灌注损伤中的作用。由CD4(+)T细胞产生的干扰素-γ诱导巨噬细胞产生肿瘤坏死因子-α，而由γ-增量T细胞分泌的IL-17A导致中性粒细胞募集。肿瘤坏死因子-α和白介素17A对星形胶质细胞的协同作用导致中性粒细胞趋化因子CXCL-1的分泌增加。卒中诱导后3小时内应用IL-17A阻断抗体可减少脑梗塞范围并改善小鼠的神经学预后。在中风患者的尸检脑组织中，我们检测到IL-17A阳性淋巴细胞，这表明炎症级联反应的这一方面也与人脑相关。我们认为，选择性靶向IL-17A信号转导可能为卒中的治疗提供新的选择。(《血色》2012；120(18)：3793-3802)
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)