Calcium-mediated shaping of naive CD4 T-cell phenotype and function

作者：Vincent Guichard, Nelly Bonilla, Aurélie Durand, Alexandra Audemard‐Verger, Thomas Guilbert, Bruno Martin, Bruno Lucas, Cédric Auffray · 发表于：eLife · 年份：2017 · DOI：10.7554/elife.27215 · 被引用次数：29 · 研究领域：Signaling Pathways in Disease、T-cell and B-cell Immunology、Immune Cell Function and Interaction

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.