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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-08-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.149346 |
| _version_ | 1811329144454119424 |
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| author | Marina Anastasiou Gail A. Newton Kuljeet Kaur Francisco J. Carrillo-Salinas Sasha A. Smolgovsky Abraham L. Bayer Vladimir Ilyukha Shruti Sharma Alexander Poltorak Francis W. Luscinskas Pilar Alcaide |
| author_facet | Marina Anastasiou Gail A. Newton Kuljeet Kaur Francisco J. Carrillo-Salinas Sasha A. Smolgovsky Abraham L. Bayer Vladimir Ilyukha Shruti Sharma Alexander Poltorak Francis W. Luscinskas Pilar Alcaide |
| author_sort | Marina Anastasiou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:38:38Z |
| format | Article |
| id | doaj.art-416b3de649144e29a5509b756c42a295 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-13T15:38:38Z |
| publishDate | 2021-08-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-416b3de649144e29a5509b756c42a2952022-12-22T02:41:12ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-08-01615Endothelial STING controls T cell transmigration in an IFNI-dependent mannerMarina AnastasiouGail A. NewtonKuljeet KaurFrancisco J. Carrillo-SalinasSasha A. SmolgovskyAbraham L. BayerVladimir IlyukhaShruti SharmaAlexander PoltorakFrancis W. LuscinskasPilar AlcaideThe 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.https://doi.org/10.1172/jci.insight.149346InflammationVascular biology |
| spellingShingle | Marina Anastasiou Gail A. Newton Kuljeet Kaur Francisco J. Carrillo-Salinas Sasha A. Smolgovsky Abraham L. Bayer Vladimir Ilyukha Shruti Sharma Alexander Poltorak Francis W. Luscinskas Pilar Alcaide Endothelial STING controls T cell transmigration in an IFNI-dependent manner JCI Insight Inflammation Vascular biology |
| title | Endothelial STING controls T cell transmigration in an IFNI-dependent manner |
| title_full | Endothelial STING controls T cell transmigration in an IFNI-dependent manner |
| title_fullStr | Endothelial STING controls T cell transmigration in an IFNI-dependent manner |
| title_full_unstemmed | Endothelial STING controls T cell transmigration in an IFNI-dependent manner |
| title_short | Endothelial STING controls T cell transmigration in an IFNI-dependent manner |
| title_sort | endothelial sting controls t cell transmigration in an ifni dependent manner |
| topic | Inflammation Vascular biology |
| url | https://doi.org/10.1172/jci.insight.149346 |
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