刺
血小板生成素
血小板
巨核细胞
细胞生物学
血小板生成素
血小板活化
干扰素基因刺激剂
信号转导
信号转导衔接蛋白
生物
化学
免疫学
先天免疫系统
免疫系统
造血
干细胞
工程类
航空航天工程
作者
Firas El-Mortada,Karima Landelouci,Samuel Bertrand-Perron,Félix-Antoine Aubé,Amy Poirier,Amel Bidias,Georges Jourdi,Mélanie Welman,Michael P. Gantier,Justin Raymond Hamilton,Benjamin T. Kile,Marie Lordkipanidzé,Geneviève Pépin
标识
DOI:10.26508/lsa.202302211
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI