TLR3是一个重要的固有免疫受体，在宿主抗病毒免疫应答以及疾病转归等方面发挥关键作用。TLR3信号需要被精确调控，过度活化往往造成组织损伤。干扰素诱导表达基因（ISG）产物介导的TLR3信号正负调控机制是天然抗病毒免疫领域研究热点之一。CD317是一个干扰素诱导表达的抗病毒蛋白，通过其独特的拓扑结构束缚囊膜病毒出膜，抑制病毒扩散。但作为一个ISG，CD317对TLR3介导的信号转导是否有调控作用，目前尚不清楚。我们前期研究发现，巨噬细胞上CD317敲减/敲除促进TLR3信号活化及I型干扰素的产生，提示CD317在TLR3信号转导过程中发挥负调控作用，极可能是机体控制抗病毒反应强度、避免组织损伤的重要负反馈机制之一。因此，本项目拟以此为切入点，系统研究CD317调控巨噬细胞TLR3信号转导的作用机制，为病毒感染或其他TLR3相关疾病的治疗提供新的靶点和理论指导。

TLR3 is an important innate immune receptor that plays crucial roles in the host's antiviral immune response and disease progression. TLR3 signaling needs to be precisely regulated, otherwise overactivation often leads to tissue damage. The mechanism of positive and negative regulation of TLR3 mediated by interferon-stimulated gene (ISG) products is one of the research hotspots in the field of antiviral innate immunity. CD317 is an interferon-induced antiviral protein, which tethers the envelope virus to the cell membrane through its unique topological structure and inhibits the spread of the virus. However, as an ISG, it is not clear whether CD317 has a regulatory effect on TLR3-mediated signaling transduction. Our previous study found that CD317 knockdown/knockout on macrophages promotes the activation of TLR3 signaling and the production of type I interferon, suggesting that CD317 plays a negative regulatory role in the TLR3 signaling pathway, which may be one of the important negative feedback mechanisms for the host to control the antiviral response intensity and avoid tissue damages. Therefore, this project intends to take this as a starting point to systematically study the mechanism of negative regulation of TLR3 signaling by CD317 on macrophages, so as to provide new targets and theoretical guidance for the treatment of viral infection or other TLR3-related diseases.