Calcium-mediated shaping of naive CD4 T-cell phenotype and function
| Autor: | Vincent Guichard, Nelly Bonilla, Aurélie Durand, Alexandra Audemard-Verger, Thomas Guilbert, Bruno Martin, Bruno Lucas, Cédric Auffray |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | eLife, Vol 6 (2017) |
| Druh dokumentu: | article |
| ISSN: | 2050-084X 29547547 |
| DOI: | 10.7554/eLife.27215 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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