Intracerebral hemorrhage(ICH)causes hematoma formation,leading to PHE,which is associated with leukocyte mobilization and increased inflammation at the site of brain injury.However,the fate of accumulated leukocytes w...Intracerebral hemorrhage(ICH)causes hematoma formation,leading to PHE,which is associated with leukocyte mobilization and increased inflammation at the site of brain injury.However,the fate of accumulated leukocytes within the hematoma and their impact on PHE expansion remain unknown.We performed single-cell immune profiling of hematoma cells from patients with acute ICH and reported a distinct phenotypic transformation of CD8^(+)T cells within the hematoma during the first 24 h after onset.In addition to enhanced IFN-γproduction and migration capacity,these CD8^(+)T cells displayed remarkable glycolytic signatures.The metabolic fitness and functional reprogramming of hematomal CD8^(+)T cells are associated with the transcription factor FOXO1.Single-cell profiling of brain-infiltrating CD8^(+)T cells within the perihematomal tissues of ICH patients and cell culture assays revealed their capacity to activate microglia via the production of IFN-γ.Furthermore,the removal of hematomal CD8^(+)T cells reduced neuroinflammation,PHE expansion and neurological deficits in ICH mice.Thus,CD8^(+)T cells undergo metabolic and functional reprogramming within the hematoma during the acute phase of ICH,which contributes to PHE formation and neurological deterioration.展开更多
基金supported in part by the National Science Foundation of China(U21A20360,82371349,82225015,82171284,82200279 and 82101373)the National Key Research and Development Project of China(2021ZD0202400)+2 种基金the National Science and Technology Major Project of China(2024ZD0527905)the New Cornerstone Science Foundation through the XPLORER PRIZE,the Science and Technology Development Fund of Tianjin Education Commission for Higher Education Grants(2021ZD035)the Major Scientific Research Program for Young and Middle-aged Health Professionals of Fujian Province(2022ZQNZD005).
文摘Intracerebral hemorrhage(ICH)causes hematoma formation,leading to PHE,which is associated with leukocyte mobilization and increased inflammation at the site of brain injury.However,the fate of accumulated leukocytes within the hematoma and their impact on PHE expansion remain unknown.We performed single-cell immune profiling of hematoma cells from patients with acute ICH and reported a distinct phenotypic transformation of CD8^(+)T cells within the hematoma during the first 24 h after onset.In addition to enhanced IFN-γproduction and migration capacity,these CD8^(+)T cells displayed remarkable glycolytic signatures.The metabolic fitness and functional reprogramming of hematomal CD8^(+)T cells are associated with the transcription factor FOXO1.Single-cell profiling of brain-infiltrating CD8^(+)T cells within the perihematomal tissues of ICH patients and cell culture assays revealed their capacity to activate microglia via the production of IFN-γ.Furthermore,the removal of hematomal CD8^(+)T cells reduced neuroinflammation,PHE expansion and neurological deficits in ICH mice.Thus,CD8^(+)T cells undergo metabolic and functional reprogramming within the hematoma during the acute phase of ICH,which contributes to PHE formation and neurological deterioration.
