Endothelial STING controls T cell transmigration in an IFNI-dependent manner.
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-α 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-α-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.
['Anastasiou|Marina|M|', 'Newton|Gail A|GA|', 'Kaur|Kuljeet|K|', 'Carrillo-Salinas|Francisco J|FJ|', 'Smolgovsky|Sasha A|SA|', 'Bayer|Abraham L|AL|', 'Ilyukha|Vladimir|V|', 'Sharma|Shruti|S|', 'Poltorak|Alexander|A|', 'Luscinskas|Francis W|FW|', 'Alcaide|Pilar|P|']
Endothelial cells Cell migration/adhesion Inflammation Vascular Biology