| First Author | Sun X | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 6182 |
| PubMed ID | 33273464 | Mgi Jnum | J:299391 |
| Mgi Id | MGI:6490854 | Doi | 10.1038/s41467-020-19941-0 |
| Citation | Sun X, et al. (2020) DNA-PK deficiency potentiates cGAS-mediated antiviral innate immunity. Nat Commun 11(1):6182 |
| abstractText | Upon sensing cytosolic DNA, the enzyme cGAS induces innate immune responses that underpin anti-microbial defenses and certain autoimmune diseases. Missense mutations of PRKDC encoding the DNA-dependent protein kinase (DNA-PK) catalytic subunit (DNA-PKcs) are associated with autoimmune diseases, yet how DNA-PK deficiency leads to increased immune responses remains poorly understood. In this study, we report that DNA-PK phosphorylates cGAS and suppresses its enzymatic activity. DNA-PK deficiency reduces cGAS phosphorylation and promotes antiviral innate immune responses, thereby potently restricting viral replication. Moreover, cells isolated from DNA-PKcs-deficient mice or patients carrying PRKDC missense mutations exhibit an inflammatory gene expression signature. This study provides a rational explanation for the autoimmunity of patients with missense mutations of PRKDC, and suggests that cGAS-mediated immune signaling is a potential target for therapeutic interventions. |
