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.
long-term brain recovery