1. Immunology and Inflammation

Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation

  1. Emilie V Russler-Germain  Is a corresponding author
  2. Jaeu Yi
  3. Shannon Young
  4. Katherine Nutsch
  5. Harikesh S Wong
  6. Teresa L Ai
  7. Jiani N Chai
  8. Vivek Durai
  9. Daniel H Kaplan
  10. Ronald N Germain
  11. Kenneth M Murphy
  12. Chyi-Song Hsieh  Is a corresponding author
  1. Washington University in St Louis, United States
  2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States
  3. University of Pittsburgh, United States
https://doi.org/10.7554/eLife.54792
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Cite this article
  1. Emilie V Russler-Germain
  2. Jaeu Yi
  3. Shannon Young
  4. Katherine Nutsch
  5. Harikesh S Wong
  6. Teresa L Ai
  7. Jiani N Chai
  8. Vivek Durai
  9. Daniel H Kaplan
  10. Ronald N Germain
  11. Kenneth M Murphy
  12. Chyi-Song Hsieh
(2021)
Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation
eLife 10:e54792.
https://doi.org/10.7554/eLife.54792
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Abstract

Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD103+ gut dendritic cells (DCs), yet their role in commensal-reactive pTreg development is unclear. Using two Helicobacter-specific T cell receptor (TCR) transgenic mouse lines, we found that both CD103+ and CD103– migratory, but not resident, DCs from the colon-draining mesenteric lymph node presented Helicobacter antigens to T cells ex vivo. Loss of most CD103+ migratory DCs in vivo using murine genetic models did not affect the frequency of Helicobacter-specific pTreg cell generation or induce compensatory tolerogenic changes in the remaining CD103– DCs. By contrast, activation in a Th1-promoting niche in vivo blocked Helicobacter-specific pTreg generation. Thus, these data suggest a model where DC-mediated effector T cell differentiation is 'dominant', necessitating that all DC subsets presenting antigen are permissive for pTreg cell induction to maintain gut tolerance.

Data availability

16S rRNA sequencing data has been deposited in ENA (PRJEB42640).

The following data sets were generated

Article and author information

Author details

  1. Emilie V Russler-Germain

    Internal Medicine, Washington University in St Louis, Saint Louis, United States
    For correspondence
    russler@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2036-6697

  2. Jaeu Yi

    Internal Medicine, Washington University in St Louis, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Shannon Young

    Internal Medicine, Washington University in St Louis, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Katherine Nutsch

    Internal Medicine, Washington University in St Louis, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Harikesh S Wong

    Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Teresa L Ai

    Internal Medicine, Washington University in St Louis, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Jiani N Chai

    Internal Medicine, Washington University in St Louis, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2560-8218

  8. Vivek Durai

    Pathology, Washington University in St Louis, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Daniel H Kaplan

    Dermatology and Immunology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Ronald N Germain

    Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1495-9143

  11. Kenneth M Murphy

    Department of Pathology and Immunology, Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  12. Chyi-Song Hsieh

    Internal Medicine, Washington University in St Louis, Saint Louis, United States
    For correspondence
    chsieh@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (R01 AI079187)

  • Chyi-Song Hsieh

National Institutes of Health (R01 AI136515)

  • Chyi-Song Hsieh

Burroughs Wellcome Fund

  • Chyi-Song Hsieh

National Institutes of Health (F30 DK111071)

  • Emilie V Russler-Germain

National Institutes of Health (T32 GM007200)

  • Emilie V Russler-Germain

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

Reviewing Editor

  1. Andrew J MacPherson, University of Bern, Switzerland

Ethics

Animal experimentation: All animal experiments were performed in strict accordance with the guidelines of the Institutional Animal Care and Use Committee at Washington University (Protocol Number: 20170036).

Version history

  1. Received: December 30, 2019
  2. Accepted: January 22, 2021
  3. Accepted Manuscript published: February 3, 2021 (version 1)
  4. Version of Record published: February 11, 2021 (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.

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  1. Emilie V Russler-Germain
  2. Jaeu Yi
  3. Shannon Young
  4. Katherine Nutsch
  5. Harikesh S Wong
  6. Teresa L Ai
  7. Jiani N Chai
  8. Vivek Durai
  9. Daniel H Kaplan
  10. Ronald N Germain
  11. Kenneth M Murphy
  12. Chyi-Song Hsieh
(2021)
Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation
eLife 10:e54792.
https://doi.org/10.7554/eLife.54792

Share this article

https://doi.org/10.7554/eLife.54792

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