Megakaryocytes possess a STING pathway that is transferred to platelets to potentiate activation.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
received:
11
06
2023
revised:
15
11
2023
accepted:
16
11
2023
medline:
24
11
2023
pubmed:
23
11
2023
entrez:
22
11
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37993259
pii: 7/2/e202302211
doi: 10.26508/lsa.202302211
pmc: PMC10665521
pii:
doi:
Substances chimiques
DNA
9007-49-2
Cytokines
0
Nucleotidyltransferases
EC 2.7.7.-
Interferon Type I
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 El-Mortada et al.
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