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

Autor:	Anastasiou M; Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.; Department of Internal Medicine, University of Crete Medical School, Crete, Greece., Newton GA; Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Kaur K; Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA., Carrillo-Salinas FJ; Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA., Smolgovsky SA; Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.; Tufts Graduate School for Biomedical Sciences Immunology Program, Tufts University School of Medicine, Boston, Massachusetts, USA., Bayer AL; Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.; Tufts Graduate School for Biomedical Sciences Immunology Program, Tufts University School of Medicine, Boston, Massachusetts, USA., Ilyukha V; Petrozavodsk State University, Petrozavodsk, Republic of Karelia, Russia., Sharma S; Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.; Tufts Graduate School for Biomedical Sciences Immunology Program, Tufts University School of Medicine, Boston, Massachusetts, USA., Poltorak A; Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.; Tufts Graduate School for Biomedical Sciences Immunology Program, Tufts University School of Medicine, Boston, Massachusetts, USA.; Petrozavodsk State University, Petrozavodsk, Republic of Karelia, Russia., Luscinskas FW; Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Alcaide P; Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.; Tufts Graduate School for Biomedical Sciences Immunology Program, Tufts University School of Medicine, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2021 Aug 09; Vol. 6 (15). Date of Electronic Publication: 2021 Aug 09.
DOI:	10.1172/jci.insight.149346
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu