Department of Neurology, North Kuanren General Hospital, Chongqing 401121, China.
State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing 400038, China.
Int Immunopharmacol. 2021 Jul;96:107678. doi: 10.1016/j.intimp.2021.107678. Epub 2021 May 24.
Through amplifying inflammatory cascades, IL-17A produced by γδ T cells potently attracts neutrophils to the site of injury for exacerbating ischemic tissue damage. Our goal was to identify the precise role of γδ T cell subsets in ischemic brain tissue damage of stroke.
In a model of experimental stroke, we analyzed the functions of Vγ1 and Vγ4 T cells on γδ T cell-mediated ischemic brain tissue damage of stroke.
We identified that, in stroke, Vγ4 T cells are essential for γδ T cell-mediated ischemic brain tissue damage through providing an early source of IL-17A. Both CCL20 and IL-1β/IL-23 are deeply involved in Vγ4 T cell-mediated amplification of inflammatory responses: CCL20 might promote Vγ4 T cells recruit to infract hemisphere, and IL-1β/IL-23 powerfully enhance IL-17A production mediated by the infiltrating Vγ4 T cells. Moreover, Vγ4 T cell-derived IL-17A enhances both CCL20 and IL-1β, and conversely, CCL20 and IL-1β further enhance both recruitment and IL-17A production of IL-17A-positive cells, in a classic positive feedback loop.
Our data suggest that in the setting of ischemic stroke, Vγ4 T cell-derived IL-17A, CCL20 and IL-1β/IL-23 in infract hemisphere coordinately to amplify inflammatory cascades and exacerbate ischemic tissue damage.
γδ T 细胞产生的白细胞介素-17A 通过放大炎症级联反应，有力地将中性粒细胞吸引到损伤部位，从而加剧缺血性组织损伤。我们的目标是确定 γδ T 细胞亚群在中风缺血性脑组织损伤中的确切作用。
在实验性中风模型中，我们分析了 Vγ1 和 Vγ4 T 细胞在 γδ T 细胞介导的中风缺血性脑组织损伤中的作用。
我们发现，在中风中，Vγ4 T 细胞通过提供 IL-17A 的早期来源，对 γδ T 细胞介导的缺血性脑组织损伤至关重要。CCL20 和 IL-1β/IL-23 都深度参与了 Vγ4 T 细胞介导的炎症反应放大：CCL20 可能促进 Vγ4 T 细胞募集到梗塞半球，而 IL-1β/IL-23 则有力地增强了浸润的 Vγ4 T 细胞介导的 IL-17A 产生。此外，Vγ4 T 细胞衍生的 IL-17A 增强了 CCL20 和 IL-1β，反之，CCL20 和 IL-1β 进一步增强了 IL-17A 阳性细胞的募集和 IL-17A 的产生，形成了一个经典的正反馈环。
我们的数据表明，在缺血性中风的情况下，梗塞半球中 Vγ4 T 细胞衍生的 IL-17A、CCL20 和 IL-1β/IL-23 协同放大炎症级联反应，加剧缺血性组织损伤。
