识别胞质DNA的cGAS-STING信号通路在宿主防御病原微生物侵染的固有免疫反应中具有关键功能，过度激活该通路也会诱发自身免疫等疾病。目前急需全面而深入地探讨：STING信号转导通路如何受到精确的调控？在预实验中，我们利用RNAi功能筛选的策略，初步发现去SUMO化酶SENP5对于cGAS-STING信号通路具有潜在的新调控功能。本项目拟从分子、细胞和疾病动物模型等层面，解析SENP5动态调节cGAS-STING信号通路的具体分子机制、揭示SENP5在抗感染和自身免疫反应中的关键功能，阐释SUMO化修饰的动态变化在固有免疫反应中的新调节作用，为预防和治疗病原体感染、自身免疫相关疾病、新型药物筛选提供新策略和新思路。

The cGAS-STING signaling pathway, which detects the presence of the aberrant cytosolic DNAs, is emerging as the essential component of the innate immunity. It is also implicated in the pathogenesis of some autoimmune disorders. The delineation of the cGAS-STING signaling and its spatial/temporal regulations represents a fast-evolving biomedical frontier. By RNAi-based screening approach, we identified the SUMO-specific protease 5 (SENP5) as a potential regulator of the cGAS-STING pathway. In this project, we aim to systematically elucidate how SENP5 modulates the cGAS-STING signaling at molecular and cellular levels, uncovering its physiological/pathological functions in anti-microbial responses or autoimune disorders, highlighting the novel function of the dynamical SUMOylation in innate immunity. The insights from the study will be instrumental for the prevention and treatment of infection and autoimmune diseases.