1. Immunology and Inflammation
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Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node

  1. Yang Zhang
  2. Theodore L Roth
  3. Elizabeth E Gray
  4. Hsin Chen
  5. Lauren B Rodda
  6. Yin Liang
  7. Patrick Ventura
  8. Saul Villeda
  9. Paul R Crocker
  10. Jason G Cyster  Is a corresponding author
  1. Howard Hughes Medical Institute, University of California, San Francisco, United States
  2. University of Washington School of Medicine, United States
  3. University of California, San Francisco, United States
  4. University of Dundee, United Kingdom
Research Article
  • Cited 36
  • Views 6,468
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Cite this article as: eLife 2016;5:e18156 doi: 10.7554/eLife.18156

Abstract

Lymph nodes (LNs) contain innate-like lymphocytes that survey the subcapsular sinus (SCS) and associated macrophages for pathogen entry. The factors promoting this surveillance behavior have not been defined. Here we report that IL7RhiCcr6+ lymphocytes in mouse LNs rapidly produce IL17 upon bacterial and fungal challenge. We show that these innate-like lymphocytes are mostly LN resident. Ccr6 is required for their accumulation near the SCS and for efficient IL17 induction. Migration into the SCS intrinsically requires S1pr1 whereas movement from the sinus into the parenchyma involves the integrin LFA1 and its ligand ICAM1. CD169, a sialic acid-binding lectin, helps retain the cells within the sinus, preventing their loss in lymph flow. These findings establish a role for Ccr6 in augmenting innate-like lymphocyte responses to lymph-borne pathogens, and they define requirements for cell movement between parenchyma and SCS in what we speculate is a program of immune surveillance that helps achieve LN barrier immunity.

Article and author information

Author details

  1. Yang Zhang

    Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Theodore L Roth

    Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3970-9573
  3. Elizabeth E Gray

    Department of Immunology, University of Washington School of Medicine, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Hsin Chen

    Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Lauren B Rodda

    Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yin Liang

    Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Patrick Ventura

    The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Saul Villeda

    The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Paul R Crocker

    Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Jason G Cyster

    Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    For correspondence
    jason.cyster@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2345-629X

Funding

Howard Hughes Medical Institute

  • Yang Zhang
  • Theodore L Roth
  • Elizabeth E Gray
  • Hsin Chen
  • Lauren B Rodda
  • Jason G Cyster

National Institutes of Health (AI074847)

  • Jason G Cyster

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animals were housed in a specific pathogen-free environment in the Laboratory Animal Research Center at the University of California San Francisco (UCSF), and all experiments conformed to the ethical principles and guidelines approved by the UCSF Institutional and Animal Care and Use Committee, protocol approval number: AN107975-02.

Reviewing Editor

  1. Ronald N Germain, National Institute of Allergy and Infectious Diseases, United States

Publication history

  1. Received: May 24, 2016
  2. Accepted: July 30, 2016
  3. Accepted Manuscript published: August 3, 2016 (version 1)
  4. Accepted Manuscript updated: August 3, 2016 (version 2)
  5. Version of Record published: September 9, 2016 (version 3)

Copyright

© 2016, Zhang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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