cGAS-IFN-I responses by extracting nuclear DNA from dying cells via nucleocytosis - PubMed
4 days ago
- #inflammatory diseases
- #cGAS-STING pathway
- #nucleocytosis
- cGAS-IFN-I responses are activated by self-DNA through a process called 'nucleocytosis', where nuclear DNA is extracted from dying cells by macrophages.
- Lysosomal malfunction, caused by proton loss and PPT1 inhibition, leads to cell death and calreticulin accumulation in the nuclei.
- Macrophages access calreticulin-enriched nuclei of dying cells to extract DNA, activating the cGAS-STING pathway.
- PPT1-targeting cationic amphiphilic drugs induce a cGAS-STING-dependent IFN-I response both in vitro and in vivo.
- Nucleocytosis is identified as a macrophage function for nuclear DNA extraction and induction of the cGAS/IFN-I axis.
- Nucleocytosis-inducing cell death could be a target for treating self-DNA-related inflammatory diseases.