Endothelial STING controls T cell transmigration in an IFNI-dependent manner.
JCI Insight
; 6(15)2021 08 09.
Article
em En
| MEDLINE
| ID: mdl-34156982
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Interferon Tipo I
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Receptor de Interferon alfa e beta
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Migração Transendotelial e Transepitelial
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Proteínas de Membrana
Limite:
Animals
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos