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

Endothelial STING controls T cell transmigration in an IFNI-dependent manner.
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DOI:
10.1172/jci.insight.149346
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发表时间:
2021-08-09
期刊:
影响因子:
8
通讯作者:
Alcaide P
Alcaide P
中科院分区:
医学1区
文献类型:
--
作者:
Anastasiou M;Newton GA;Kaur K;Carrillo-Salinas FJ;Smolgovsky SA;Bayer AL;Ilyukha V;Sharma S;Poltorak A;Luscinskas FW;Alcaide P

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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.
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