Long Lu1, Yangping Wang2, Lina Zhou3, Yashu Li2, Xiaorong Zhang4, Xiaohong Hu4, Shugui Shi5, Weifeng He6. 1. Department of Neurology, North Kuanren General Hospital, Chongqing 401121, China. 2. 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. 3. Department of Endocrinology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. 4. 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; Chongqing Key Laboratory for Disease Proteomics, Chongqing 400038, China. 5. Department of Neurology, North Kuanren General Hospital, Chongqing 401121, China. Electronic address: shishg@yeah.net. 6. 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; Chongqing Key Laboratory for Disease Proteomics, Chongqing 400038, China. Electronic address: whe761211@hotmail.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.