γδ T cells aggravate blood-brain-barrier injury via IL-17A in experimental ischemic stroke.

BACKGROUND:γδ T cells were reported to play a key role in ischemic stroke. The integrity of the blood-brain barrier (BBB) directly affects the prognosis of ischemic stroke. This study aimed to determine whether γδ T cells aggravate BBB injury and determine the outcome of ischemic stroke. METHODS:Oxygen-glucosedeprivation (OGD) and middle cerebral artery occlusion (MCAO) were used as ischemic stroke models in vitro and in vivo. Flow cytometry was used to evaluate the intracranial infiltration of γδ T cells. RT-qPCR was used to evaluatethe mRNA levels of cytokines and γδ T cell markers. ELISA was used to test the levels of cytokines. Immunofluorescence, TEER and western blotting were used to measure BBB injury. RESULTS:In this study, we found that a large number of γδ T cells infiltrated the ischemic penumbra 24 h after MCAO. Knockout of γδ T cells improved the motor function injury induced by MCAO and significantly reduced the volume of cerebral infarction and blood-brain barrier injury. IL-17A neutralization could rescue the BBB injury induced by γδ T cells both in vitro and in vivo. CONCLUSIONS:Peripheral γδ T cells immediately infiltrated into the lesion site after ischemic stroke and aggravated BBB injury by releasing IL-17A, which might be a potential therapeutic target for ischemic stroke.