cGAS-STING轴将DNA损伤和细胞压力与I型干扰素（IFN）信号转导相结合，促进炎性应激反应下的转录变化。cGAS-STING通路对胞质中的dsDNA、微核以及LINE-1（L1）可逆转座子形式的DNA做出反应。L1转座子是一类在我们的基因组中保持高度活跃的自我复制的非LTR转座子。L1转座子逐渐成为cGAS-STING和干扰素信号转导的重要诱发因子，这些因子在包括癌症在内的多种疾病中经常发生异常。cGAS-STING和L1活性的一个关键抑制因子是外切酶TREX1，而TREX1的失活则促进L1的积累。此外，在慢性诱导cGAS-STING信号转导的一些疾病中，如Aicardi-Goutières综合征、Fanconi贫血和皮肌炎，L1失调正成为常见的关键问题。尽管TREX1在四足动物物种中高度保守，但还有其他抑制L1反转座的抑制蛋白存在。这些抑制基因在突变时通常与表现为未受限制的炎症相关的疾病有关，这些疾病与高度活跃的cGAS-STING活性和升高的L1表达水平有关。在本综述中，我们讨论了这些相互关联的L1抑制通路及其在疾病中调控cGAS-STING和炎症的作用。

The cGAS-STING axis integrates DNA damage and cellular stress with type I interferon (IFN) signalling to facilitate transcriptional changes underlying inflammatory stress responses. The cGAS-STING pathway responds to cytosolic DNA in the form of dsDNA, micronuclei, and LINE-1 (L1) retroelements. L1 retroelements are a class of self-propagating non-LTR transposons that have remained highly active in our genomes. L1 retroelements are emerging as important inducers of cGAS-STING and interferon signalling, which are often dysregulated in several diseases including cancer. A key repressor of cGAS-STING and L1 activity is the exonuclease TREX1, and loss of TREX1 promotes the accumulation of L1. In addition, L1 dysregulation is becoming a common theme among diseases with chronic induction of type I IFN signalling through cGAS-STING such as Aicardi-Goutières syndrome, Fanconi anemia, and Dermatomyotisis. Although TREX1 is highly conserved in tetrapod species, other suppressor proteins exist that inhibit L1 retrotransposition. These suppressor genes when mutated are often associated with diseases characterized by unchecked inflammation that is associated with high cGAS-STING activity and elevated levels of L1 expression. In this review, we discuss these interconnected pathways of L1 suppression, and their role in the regulation of cGAS-STING and inflammation in disease.