C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation

ELife
Chang Hoon LeeJoshua M Farber

Abstract

Many mediators and regulators of extravasation by bona fide human memory-phenotype T cells remain undefined. Mucosal-associated invariant T (MAIT) cells are innate-like, antibacterial cells that we found excelled at crossing inflamed endothelium. They displayed abundant selectin ligands, with high expression of FUT7 and ST3GAL4, and expressed CCR6, CCR5, and CCR2, which played non-redundant roles in trafficking on activated endothelial cells. MAIT cells selectively expressed CCAAT/enhancer-binding protein delta (C/EBPδ). Knockdown of C/EBPδ diminished expression of FUT7, ST3GAL4 and CCR6, decreasing MAIT cell rolling and arrest, and consequently the cells' ability to cross an endothelial monolayer in vitro and extravasate in mice. Nonetheless, knockdown of C/EBPδ did not affect CCR2, which was important for the step of transendothelial migration. Thus, MAIT cells demonstrate a program for extravasastion that includes, in part, C/EBPδ and C/EBPδ-regulated genes, and that could be used to enhance, or targeted to inhibit T cell recruitment into inflamed tissue.

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Citations

Jan 17, 2020·European Journal of Immunology·Marion SchneiderJames E Ussher
Jan 28, 2020·Annual Review of Immunology·Nicholas M Provine, Paul Klenerman
Dec 7, 2018·The Journal of Experimental Medicine·Marion SalouOlivier Lantz
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Oct 15, 2020·Immunity·François LegouxOlivier Lantz
Nov 2, 2021·Soft Matter·Long LiAna-Sunčana Smith

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Methods Mentioned

BETA
flow cytometry and
flow cytometry
confocal microscopy
glycosylation
transfections
immunoprecipitation
ChIP
ChIP-PCR
transfection
protein assay

Software Mentioned

Imaris
ImageJ
GraphPad
Adobe Photoshop
Prism
Genomatix Genome Analyzer
Common TF
SA

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