cGAS-STING通路是核心的胞质DNA识别通路，通过识别病毒DNA、调控I型干扰素和炎症因子产生，参与抗病毒天然免疫应答；亦可识别自身异常DNA导致自身免疫性疾病，还可识别肿瘤来源的DNA诱导抗肿瘤免疫应答，甚至直接调控肿瘤细胞增殖和衰老。cGAS-STING通路与多种疾病的发生发展密切相关，如何精确调控cGAS-STING通路以获得有益的作用是重要的前沿性科学问题。我们前期研究发现定位于内质网的E3泛素连接酶TRIM13在巨噬细胞内负向调节DNA病毒诱导的天然免疫应答。我们提出科学假设：TRIM13可能通过调控STING的泛素化修饰影响STING的功能。我们将借助于TRIM13基因敲除小鼠和细胞系，利用DNA病毒体内外感染模型确立TRIM13负向调控STING的效应和分子机制。该研究将为cGAS-STING的调控提供新机制，并为病理性DNA相关疾病的防治提供新思路和潜在靶点。

The cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) signaling pathway is the central pathway in sensing cytosolic DNA. cGAS-STING pathway can regulate the antiviral innate immune response by promoting the production of type I interferon and inflammatory cytokines after sensing of viral DNA. It can also cause autoimmune diseases in case sensing abnormal self DNA, or induce anti-tumor immunity in case sensing tumor-derived DNA. Moreover, the cGAS-STING pathway has been indicated to directly regulate the proliferation and senescence of tumor cells. Therefore the cGAS-STING pathway has been closely related to the initiation and progression of various diseases, and it has been a leading scientific question how to effectively manipulate the cGAS-STING pathway for more beneficial effects. Our preliminary studies have shown that the E3 ubiquitin ligase TRIM13 (tripartite motif containing 13) is localized in endoplasmic reticulum and can negatively regulate the antiviral innate immune response upon DNA virus infection. So we propose that TRIM13 may affect the roles of STING by regulating the ubiquitin modification of STING. We aim to reveal the effects and the associated molecular mechanisms for TRIM13-mediated negative regulation of STING, taking advantages of the established TRIM13 knockout mice and cell lines as well as the in vitro and in vivo models of DNA virus infection. Our study will provide insights for the mechanical control of the cGAS-STING signaling pathway, and may provide new strategy and potential target for the prevention and treatment of pathogenic DNA-associated diseases.