V Gamma 4 T Cell-Derived Il-17a Is Essential For Amplification Of Inflammatory Cascades In Ischemic Brain Tissue After Stroke

Background: Through amplifying inflammatory cascades, IL-17A produced by gamma delta T cells potently attracts neutrophils to the site of injury for exacerbating ischemic tissue damage. Our goal was to identify the precise role of gamma delta T cell subsets in ischemic brain tissue damage of stroke.Methods: In a model of experimental stroke, we analyzed the functions of V gamma 1 and V gamma 4 T cells on gamma delta T cell-mediated ischemic brain tissue damage of stroke.Results: We identified that, in stroke, V gamma 4 T cells are essential for gamma delta T cell-mediated ischemic brain tissue damage through providing an early source of IL-17A. Both CCL20 and IL-1 beta/IL-23 are deeply involved in V gamma 4 T cellmediated amplification of inflammatory responses: CCL20 might promote V gamma 4 T cells recruit to infract hemisphere, and IL-1 beta/IL-23 powerfully enhance IL-17A production mediated by the infiltrating V gamma 4 T cells. Moreover, V gamma 4 T cell-derived IL-17A enhances both CCL20 and IL-1 beta, and conversely, CCL20 and IL-1 beta further enhance both recruitment and IL-17A production of IL-17A-positive cells, in a classic positive feedback loop.Conclusion: Our data suggest that in the setting of ischemic stroke, V gamma 4 T cell-derived IL-17A, CCL20 and IL-1 beta/IL-23 in infract hemisphere coordinately to amplify inflammatory cascades and exacerbate ischemic tissue damage.