Calcium-mediated shaping of naive CD4 T-cell phenotype and function
- Institut Cochin - Inserm U1016-CNRS UMR8104-Université Paris Descartes, France
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.
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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.
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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Calcium-mediated shaping of naive CD4 T-cell phenotype and function
eLife 6:e27215.
https://doi.org/10.7554/eLife.27215
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