| First Author | Anastasiou M | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 15 | PubMed ID | 34156982 |
| Mgi Jnum | J:313006 | Mgi Id | MGI:6793004 |
| Doi | 10.1172/jci.insight.149346 | Citation | Anastasiou M, et al. (2021) Endothelial STING controls T cell transmigration in an IFNI-dependent manner. JCI Insight 6(15) |
| abstractText | The stimulator of IFN genes (STING) protein senses cyclic dinucleotides released in response to double-stranded DNA and functions as an adaptor molecule for type I IFN (IFNI) signaling by activating IFNI-stimulated genes (ISG). We found impaired T cell infiltration into the peritoneum in response to TNF-alpha in global and EC-specific STING-/- mice and discovered that T cell transendothelial migration (TEM) across mouse and human endothelial cells (EC) deficient in STING was strikingly reduced compared with control EC, whereas T cell adhesion was not impaired. STING-/- T cells showed no defect in TEM or adhesion to EC, or immobilized endothelial cell-expressed molecules ICAM1 and VCAM1, compared with WT T cells. Mechanistically, CXCL10, an ISG and a chemoattractant for T cells, was dramatically reduced in TNF-alpha-stimulated STING-/- EC, and genetic loss or pharmacologic antagonisms of IFNI receptor (IFNAR) pathway reduced T cell TEM. Our data demonstrate a central role for EC-STING during T cell TEM that is dependent on the ISG CXCL10 and on IFNI/IFNAR signaling. |
