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

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 e...

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Autores principales: Lee, Chang Hoon, Zhang, Hongwei H, Singh, Satya P, Koo, Lily, Kabat, Juraj, Tsang, Hsinyi, Singh, Tej Pratap, Farber, Joshua M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869018/
https://www.ncbi.nlm.nih.gov/pubmed/29469805
http://dx.doi.org/10.7554/eLife.32532
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author Lee, Chang Hoon
Zhang, Hongwei H
Singh, Satya P
Koo, Lily
Kabat, Juraj
Tsang, Hsinyi
Singh, Tej Pratap
Farber, Joshua M
author_facet Lee, Chang Hoon
Zhang, Hongwei H
Singh, Satya P
Koo, Lily
Kabat, Juraj
Tsang, Hsinyi
Singh, Tej Pratap
Farber, Joshua M
author_sort Lee, Chang Hoon
collection PubMed
description 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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spelling pubmed-58690182018-03-28 C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation Lee, Chang Hoon Zhang, Hongwei H Singh, Satya P Koo, Lily Kabat, Juraj Tsang, Hsinyi Singh, Tej Pratap Farber, Joshua M eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2018-02-22 /pmc/articles/PMC5869018/ /pubmed/29469805 http://dx.doi.org/10.7554/eLife.32532 Text en http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Immunology and Inflammation
Lee, Chang Hoon
Zhang, Hongwei H
Singh, Satya P
Koo, Lily
Kabat, Juraj
Tsang, Hsinyi
Singh, Tej Pratap
Farber, Joshua M
C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation
title C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation
title_full C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation
title_fullStr C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation
title_full_unstemmed C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation
title_short C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation
title_sort c/ebpδ drives interactions between human mait cells and endothelial cells that are important for extravasation
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869018/
https://www.ncbi.nlm.nih.gov/pubmed/29469805
http://dx.doi.org/10.7554/eLife.32532
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