Year: 2021
Type: preprint
Abstract: The DNA sensor cyclic GMP-AMP synthase (cGAS) is important for antiviral and anti-tumor immunity. cGAS generates cyclic GMP-AMP (cGAMP), a diffusible cyclic dinucleotide that activates the antiviral response through the adapter protein Stimulator of Interferon Genes (STING). cGAMP is negatively charged and cannot passively cross cell membranes, but recent advances have established a role for extracellular cGAMP as an “immunotransmitter” that can be imported into cells. However, the mechanism by which cGAMP exits cells remains unknown. Here, we identify ABCC1/MRP1 as an ATP-dependent cGAMP exporter that influences STING signaling and type I interferon production. We demonstrate that ABCC1 deficiency exacerbates cGAS-dependent autoimmunity in the Trex1 -/- mouse model of Aicardi-Goutières syndrome. These studies identify ABCC1-mediated cGAMP export as a key regulatory mechanism of the cGAS-STING pathway.
Institution: University of Washington
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Award: G3353230889
OpenAlex ID: W4200216693