2020-07-222024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/700518摘要：顱內腦實質出血為一種極具破壞性的腦中風型式，伴隨著高死亡率和極差的長期癒後。至今仍未有已被核准的治療策略，可供有效改善腦出血的癒後情形。先天性及後天性免疫細胞活化所誘發的免疫反應，在腦出血病理進程有相當程度的主導地位。而具有多種亞型轉變的組織性和血源性巨噬細胞，亦提供出血腦中產生促發炎反應、血塊清除和神經修復…等等自然防衛機轉。促進巨噬細胞保護性亞型轉變也證實可減緩腦出血造成的腦部傷害。但目前對於透過何種機轉可以有效促進腦中巨噬細胞保護性亞型轉變的知識仍屬有限。調節性T和B細胞在維持免疫恆定上扮演重要角色，並可確保免疫細胞執行特定病理情況下，適妥切合的免疫反應。雖然調節性T和B細胞在出血腦中被認為具有保護功能，但調節性T細胞對於腦出血後的長期修復作用及其機制仍未被探討。在此為期一年的計劃中，我們著重探討調節性T和B細胞是否必須間接透過巨噬細胞功能來達到促進腦出血長期腦部神經功能恢復，而此調節性T和B細胞對巨噬細胞功能的調節，是否由促進該細胞保護性亞型轉變來達到。本計畫執行成果將有助於拓展在急性腦傷害架構下對調節性T細胞及先天性和後天性免疫細胞交互作用的知識，發展以神經免疫學為基礎針對腦出血的治療策略。 <br> Abstract: Intracerebral hemorrhage (ICH) is one of the most devastating types of stroke with the highest mortality rate and the worst long-term outcome and no effective medical therapeutics is currently available for treating ICH. Immune response is the predominant pathological process after ICH, which is mainly mediated by the activation of innate and acquired immune cells in the hemorrhagic region. The wide phenotypic spectrum of activated tissue-resident and blood-derived macrophages contribute to triggering self-defense mechanism that involves inflammation, hematoma clearance, and neuronal repair in the ICH brain. Promoting the transition of macrophages from traditional proinflammatory phenotype to the reparative phenotype has shown to reduce ICH brain damage. Nonetheless, our knowledge on the mechanism that facilitates such reparative phenotype in ICH remains scarce. While regulatory T (Treg) and B (Breg) cells are crucial for maintaining immune homeostasis and act as a cellular checkpoint to ensure proper functions of immune cells, pilot studies have suggested their beneficial role in acute ICH. Yet, whether Treg cells can enhance long-term ICH brain recovery and the underlying mechanism remains unknown. This one-year grant sets out to address the previously mentioned knowledge gaps in two aims. First, we will test whether manipulation of Treg and Breg cell population affects macrophages alternative activation and long-term ICH outcomes. We will further investigate whether the beneficial function of Treg cells is dependent on the effector reactions of macrophages and the underlying mechanism. Overall, this work aims to discover potential mechanisms underlying Treg/Breg-mediated long-term ICH recovery and explore the therapeutic potential of applying regulatory T/or B cell-based therapy in ICH animal models. This work will advance our knowledge not only on the function of Treg/Breg cells but also the interaction between innate and adaptive immunity in acute sterile brain injury. Our work will provide new insights for targeting immune system in successful treatment of ICH.顱內出血調節性免疫細胞巨噬細胞血塊清除長期腦部修復神經免疫學Intracerebral hemorrhageregulatory cellsmacrophageshematoma resolutionlong-term brain recoveryneuroimmunology