小胶质细胞（MG）是颅脑创伤（TBI）炎症免疫调控的关键靶点。DcR3是一种具有抗凋亡效应的多效免疫调节因子，能诱导巨噬细胞向M2表型转换，但关键机制不清；且缺乏直接证据支持其同样介导MG表型调控。在临床研究中，本课题组发现高水平血清DcR3预示TBI患者神经功能恢复良好，初步揭示DcR3的神经保护作用。结合关于caspase信号参与MG表型调控的最新报道，可推测DcR3经抑制caspase通路而介导MG的M2表型转换。为验证假说，本项目拟首先通过体外细胞实验，研究DcR3干预下MG表型、功能变化及相关分子机制，聚焦于caspase-8-caspase-3-PKC-δ/PARP通路对MG表型的影响；其次构建小鼠控制性皮层损伤模型，从动物在体水平研究DcR3神经保护功能。该项目将为实现DcR3的临床转化提供理论依据，为TBI炎症免疫调控提供新的策略。

Microglia (MG) acts as a key therapeutic target in the inflammatory regulation of traumatic brain injury (TBI). Decoy receptor 3 (DcR3) has been shown to be a potent pleiotropic immunomodulator that inhibits apoptosis and skews macrophage into M2 phenotype. However, the core mechanism of its effect in skewing macrophage into M2 phenotype is uncovered yet. And there is no direct evidence to support the role of DcR3 in mediating MG phenotypic transformation. Our previous study have demonstrated that higher levels of serum DcR3 was correlated with more favorable neurological outcomes in patients, which implied its neuroprotective effect. Taken together with the latest research involving caspase signals in MG phenotypic regulation, it is plausible that DcR3 skews MG toward M2 phenotype by inhibiting the caspase pathway. To validate the hypothesis, firstly we will investigate MG phenotype, functional changes and related molecular mechanisms by administering DcR3 in vitro, focusing on the effect of caspase-8-caspase-3-PKC-δ/PARP pathway on MG phenotype. Secondly a controlled cortical impact model will be established to study neuroprotective function of DcR3 in vivo. The project will provide a theoretical basis for the clinical translation of DcR3, and offer a new strategy for TBI inflammatory immune regulation.