CGAS activation in classical dendritic cells causes autoimmunity in TREX1-deficient mice.

ABSTRACT: Detection of cytosolic DNA by the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway provides immune defense against pathogens and cancer but can also cause autoimmunity when overactivated. The exonuclease three prime repair exonuclease 1 (TREX1) degrades DNA in the cytosol and prevents cGAS activation by self-DNA. Loss-of-function mutations of the TREX1 gene are linked to autoimmune diseases such as Aicardi-Goutières syndrome, and mice deficient in TREX1 develop lethal inflammation in a cGAS-dependent manner. In order to determine the type of cells in which cGAS activation drives autoinflammation, we generated conditional cGAS knockout mice on the Trex1^-/- background. Here, we show that genetic ablation of the cGAS gene in classical dendritic

SUBMITTER: Li T 

PROVIDER: S-EPMC11420187 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature