1. Immunology and Inflammation
Download icon

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

  1. Chang Hoon Lee
  2. Hongwei H Zhang
  3. Satya P Singh
  4. Lily Koo
  5. Juraj Kabat
  6. Hsinyi Tsang
  7. Tej Pratap Singh
  8. Joshua M Farber  Is a corresponding author
  1. National Institute of Allergy and Infectious Diseases, United States
Research Article
  • Cited 11
  • Views 1,412
  • Annotations
Cite this article as: eLife 2018;7:e32532 doi: 10.7554/eLife.32532

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, anti-bacterial 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.

Article and author information

Author details

  1. Chang Hoon Lee

    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8953-9069
  2. Hongwei H Zhang

    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Satya P Singh

    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lily Koo

    Research Technologies Branch, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Juraj Kabat

    Research Technologies Branch, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Hsinyi Tsang

    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Tej Pratap Singh

    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Joshua M Farber

    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    For correspondence
    jfarber@niaid.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3224-0378

Funding

National Institutes of Health (Intramural Research Program)

  • Joshua M Farber

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. NIAID approved submission per standard Institute procedures.

Ethics

Animal experimentation: Mice were housed under specific pathogen free conditions at the National Institutes of Health in an American Association for the Accreditation of Laboratory Animal Care-approved facility. Animals were studied under protocol LMI-13 as approved by the Animal Care and Use Committee, NIAID, NIH.

Human subjects: Human blood cells were obtained by the Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, under protocol 99-CC-0168 approved by the Institutional Review Board. Informed consent was obtained after explanation of the risks.

Reviewing Editor

  1. Wayne M Yokoyama, Howard Hughes Medical Institute, Washington University School of Medicine, United States

Publication history

  1. Received: October 6, 2017
  2. Accepted: February 21, 2018
  3. Accepted Manuscript published: February 22, 2018 (version 1)
  4. Version of Record published: March 26, 2018 (version 2)

Copyright

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.

Metrics

  • 1,412
    Page views
  • 226
    Downloads
  • 11
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)