Low-Voltage-Activated CaV3.1 Calcium Channels Shape T Helper Cell Cytokine Profiles

Immunity. 2016 Apr 19;44(4):782-94. doi: 10.1016/j.immuni.2016.01.015. Epub 2016 Mar 29.

Abstract

Activation of T cells is mediated by the engagement of T cell receptors (TCRs) followed by calcium entry via store-operated calcium channels. Here we have shown an additional route for calcium entry into T cells-through the low-voltage-activated T-type CaV3.1 calcium channel. CaV3.1 mediated a substantial current at resting membrane potentials, and its deficiency had no effect on TCR-initiated calcium entry. Mice deficient for CaV3.1 were resistant to the induction of experimental autoimmune encephalomyelitis and had reduced productions of the granulocyte-macrophage colony-stimulating factor (GM-CSF) by central nervous system (CNS)-infiltrating T helper 1 (Th1) and Th17 cells. CaV3.1 deficiency led to decreased secretion of GM-CSF from in vitro polarized Th1 and Th17 cells. Nuclear translocation of the nuclear factor of activated T cell (NFAT) was also reduced in CaV3.1-deficient T cells. These data provide evidence for T-type channels in immune cells and their potential role in shaping the autoimmune response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Animals
  • Autoimmunity / genetics
  • Autoimmunity / immunology
  • Calcium / metabolism
  • Calcium Channels, T-Type / genetics*
  • Cytokines / immunology
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NFATC Transcription Factors / metabolism*
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*

Substances

  • Cacna1g protein, mouse
  • Calcium Channels, T-Type
  • Cytokines
  • NFATC Transcription Factors
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Calcium