title: Low-Voltage-Activated CaV3.1 Calcium Channels Shape T Helper Cell Cytokine Profiles.
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.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Huiyun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Xuexin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xue
authors.affiliation: Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Jouvin
authors.affiliation: Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Putney
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Anderson
authors.affiliation: Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Trebak
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA. Electronic address: jkinet2@me.com.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kinet
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000235:genetics*; D016207:Cytokines / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type; D016207:Cytokines; D050778:NFATC Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002118:Calcium