Platelet STING agonism and venous thrombosis: translational implications for improved disease outcomes.

Keywords: cGAS; coagulopathy; neutrophil extracellular traps; neutrophils; palmitoylation; platelets; sepsis; stimulator of interferon genes; STING agonist; STXBP2; targeted therapy; thrombin; vasculature EN cGAS coagulopathy neutrophil extracellular traps neutrophils palmitoylation platelets sepsis stimulator of interferon genes STING agonist STXBP2 targeted therapy thrombin vasculature 195 198 4 10/10/23 20230901 NES 230901 Protective host innate and adaptive immune responses to insult by pathogens and oncogenesis are multicomponent and multifaceted in nature, with excessive and/or sustained inflammatory responses leading to untoward consequences. A range of additional STING inhibitors targeting its palmitoylation site (C-176, C-178, BPK-25, and NO SB 2 sb -fatty acids), inhibiting cGAMP binding to STING (Compound 18, Astin C, SN-011) or degrading STING (SP23), have been developed,[8] which would be anticipated to ameliorate STING-induced VTE in the infectious disease, autoimmune, and cancer settings. CGAMP treatment of control platelets surprisingly selectively induced the palmitoylation (but not phosphorylation, sumoylation, or ubiquitination) of STING molecules in control platelets, with no evidence for conventional STING-TBK1-IRF3 signaling pathway activation. [Extracted from the article]