Vγ4 T cell-derived IL-17A is essential for amplification of inflammatory cascades in ischemic brain tissue after stroke

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.