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Endothelial STING controls T cell transmigration in an IFNI-dependent manner.

ABSTRACT: 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.

SUBMITTER: Anastasiou M

PROVIDER: S-EPMC8410041 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Endothelial STING controls T cell transmigration in an IFNI-dependent manner.

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

JCI insight 20210809 15

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 compa ...[more]

PMID: 34156982

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Dataset Information

Endothelial STING controls T cell transmigration in an IFNI-dependent manner.

Publications

Endothelial STING controls T cell transmigration in an IFNI-dependent manner.

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