The cytosolic Three prime Repair EXonuclease 1 (TREX1) is a powerful DNA-degrading enzyme required for clearing cytosolic DNA to prevent aberrant inflammation and autoimmunity. In the absence of TREX1 activity, cytosolic DNA pattern recognition receptors of the innate immune system are constitutively activated by undegraded TREX1 substrates. This triggers a chronic inflammatory response in humans expressing mutant TREX1 alleles, eliciting a spectrum of rare autoimmune diseases dependent on the nature of the mutation. The precise origins of cytosolic DNA targeted by TREX1 continue to emerge, but DNA emerging from the nucleus or taken up by the cell could represent potential sources. In this Review, we explore the biochemical and immunological data supporting the role of TREX1 in suppressing cytosolic DNA sensing, and discuss the possibility that TREX1 may contribute to maintenance of genome integrity.

胞质Ť重稀土素修复核酸外切酶1（TREX1）是用于清除胞质DNA，以防止异常的炎症和自身免疫所需的强大的DNA降解酶。在没有TREX1活性的情况下，先天性免疫系统的胞质DNA模式识别受体被未降解的TREX1底物组成性激活。这会在表达突变体TREX1的人类中引发慢性炎症反应等位基因，引发一系列罕见的自身免疫性疾病，具体取决于突变的性质。TREX1靶向的胞质DNA的确切来源继续出现，但是从细胞核中出现或被细胞吸收的DNA可能代表了潜在的来源。在这篇综述中，我们探讨了支持TREX1在抑制胞质DNA感应中的作用的生化和免疫学数据，并讨论了TREX1可能有助于维持基因组完整性的可能性。