1. Immunology and Inflammation
  2. Cell Biology
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Calcium-mediated shaping of naive CD4 T-cell phenotype and function

  1. Vincent Guichard
  2. Nelly Bonilla
  3. Aurélie Durand
  4. Alexandra Audemard-Verger
  5. Thomas Guilbert
  6. Bruno Martin
  7. Bruno Lucas
  8. Cédric Auffray  Is a corresponding author
  1. Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, France
Research Article
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Cite as: eLife 2017;6:e27215 doi: 10.7554/eLife.27215

Abstract

Continuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced/peripheral regulatory T cells. To decipher the molecular mechanisms governing this process, we here focus on the TCR signaling cascade and demonstrate that a rise in intracellular calcium levels is sufficient to modulate the phenotype of mouse naive CD4 T cells and to increase their sensitivity to regulatory T-cell polarization signals, both processes relying on Calcineurin activation. Accordingly, in vivo Calcineurin inhibition leads the most Self-reactive naive CD4 T cells to adopt the phenotype of their less Self-reactive cell-counterparts. Collectively, our findings demonstrate that calcium-mediated activation of the Calcineurin pathway acts as a rheostat to shape both the phenotype and effector potential of naive CD4 T cells in the steady-state.

Article and author information

Author details

  1. Vincent Guichard

    Infection, Immunity and Inflammation, Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-0206-4924
  2. Nelly Bonilla

    Infection, Immunity and Inflammation, Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Aurélie Durand

    Infection, Immunity and Inflammation, Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexandra Audemard-Verger

    Infection, Immunity and Inflammation, Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Thomas Guilbert

    Cell Biology of Host Pathogens Interactions, Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Bruno Martin

    Infection, Immunity and Inflammation, Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Bruno Lucas

    Infection, Immunity and Inflammation, Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Cédric Auffray

    Infection, Immunity and Inflammation, Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, Paris, France
    For correspondence
    cedric.auffray@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-1012-0132

Funding

Institut National de la Santé et de la Recherche Médicale

  • Nelly Bonilla
  • Alexandra Audemard-Verger
  • Thomas Guilbert
  • Bruno Martin
  • Bruno Lucas
  • Cédric Auffray

Agence Nationale de la Recherche (ANR-15-CE15-0009-01)

  • Cédric Auffray

Fondation pour la Recherche Médicale

  • Bruno Lucas

Ligue Contre le Cancer

  • Alexandra Audemard-Verger

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

Ethics

Animal experimentation: Experiments were carried out in accordance with the guidelines of the French Veterinary Department. All procedures performed were approved by the Paris-Descartes Ethical Committee for Animal Experimentation (decision CEEA34.CA.080.12). Sample sizes were chosen to ensure the reproducibility of the experiments and according to the 3Rs of animal ethics regulation.

Reviewing Editor

  1. Michael L Dustin, Reviewing Editor, University of Oxford, United Kingdom

Publication history

  1. Received: March 27, 2017
  2. Accepted: November 23, 2017
  3. Accepted Manuscript published: December 14, 2017 (version 1)
  4. Version of Record published: December 29, 2017 (version 2)
  5. Version of Record updated: January 2, 2018 (version 3)

Copyright

© 2017, Guichard 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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