10/10 EC-specific deletion of STING or a global deletion of STAT1 not only block the interferon-like response, but decrease the severity of the response to LPS

9/10 The transcriptional response involves IRF1, through a mechanism we do not yet fully understand

8/10 In parallel, IL-6 leads to mitochondrial dysfunction and mtDNA release that leads to cGAS/STING signaling

7/10 Notably, this response does not require an autocrine IFN signaling, but is a direct transcriptional response to IL-6

6/10 In vitro work showed that IL-6 leads to an IFN-like response that requires expression of STAT1, but not the canonical STAT3

5/10 This IFN signature was further increased by the deletion of the IL-6 signaling inhibitor SOCS3 in the endothelium

4/10 Analysis of the response to LPS suggested a strong interferon activation

3/10 This enables great enrichment of endothelial RNA

2/10 To better understand how endothelial cells respond to a cytokine storm, we performed endothelial-specific translating ribosome affinity purification (TRAP) on endotoxemic mice

1/10 Shock drives vascular dysfunction, with in turn leads to organ injury and potentially death, by inducing a ‘cytokine storm’. Chief among them, IL-6 is an excellent marker for septic shock severity and predicts for mortality