| First Author | El-Mortada F | Year | 2024 |
| Journal | Life Sci Alliance | Volume | 7 |
| Issue | 2 | PubMed ID | 37993259 |
| Mgi Jnum | J:342956 | Mgi Id | MGI:7560841 |
| Doi | 10.26508/lsa.202302211 | Citation | El-Mortada F, et al. (2024) Megakaryocytes possess a STING pathway that is transferred to platelets to potentiate activation. Life Sci Alliance 7(2) |
| abstractText | Platelets display unexpected roles in immune and coagulation responses. Emerging evidence suggests that STING is implicated in hypercoagulation. STING is an adaptor protein downstream of the DNA sensor cyclic GMP-AMP synthase (cGAS) that is activated by cytosolic microbial and self-DNA during infections, and in the context of loss of cellular integrity, to instigate the production of type-I IFN and pro-inflammatory cytokines. To date, whether the cGAS-STING pathway is present in platelets and contributes to platelet functions is not defined. Using a combination of pharmacological and genetic approaches, we demonstrate here that megakaryocytes and platelets possess a functional cGAS-STING pathway. Our results suggest that in megakaryocytes, STING stimulation activates a type-I IFN response, and during thrombopoiesis, cGAS and STING are transferred to proplatelets. Finally, we show that both murine and human platelets contain cGAS and STING proteins, and the cGAS-STING pathway contributes to potentiation of platelet activation and aggregation. Taken together, these observations establish for the first time a novel role of the cGAS-STING DNA sensing axis in the megakaryocyte and platelet lineage. |
