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C/EBP? drives interactions between human MAIT cells and endothelial cells that are important for extravasation.


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/EBP?). Knockdown of C/EBP? 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/EBP? 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/EBP? and C/EBP?-regulated genes, and that could be used to enhance, or targeted to inhibit T cell recruitment into inflamed tissue.

SUBMITTER: Lee CH 

PROVIDER: S-EPMC5869018 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Lee Chang Hoon CH   Zhang Hongwei H HH   Singh Satya P SP   Koo Lily L   Kabat Juraj J   Tsang Hsinyi H   Singh Tej Pratap TP   Farber Joshua M JM  

eLife 20180222


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 <i>FUT7</i> and <i>ST3GAL4</i>, and expressed CCR6, CCR5, and CCR2, which played non-redundant roles in trafficking on activated endothelial cells. MAIT cells selectively expressed CCAAT/  ...[more]

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