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

Huiyun Wang; Xuexin Zhang; Li Xue; Juan Xing; Marie Hélène Jouvin; James W. Putney; Matthew P. Anderson; Mohamed Trebak; Jean Pierre Kinet

doi:10.1016/j.immuni.2016.01.015

Low-Voltage-Activated Ca_V3.1 Calcium Channels Shape T Helper Cell Cytokine Profiles

Huiyun Wang, Xuexin Zhang, Li Xue, Juan Xing, Marie Hélène Jouvin, James W. Putney, Matthew P. Anderson, Mohamed Trebak, Jean Pierre Kinet

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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 Ca_V3.1 calcium channel. Ca_V3.1 mediated a substantial current at resting membrane potentials, and its deficiency had no effect on TCR-initiated calcium entry. Mice deficient for Ca_V3.1 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. Ca_V3.1 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 Ca_V3.1-deficient T cells. These data provide evidence for T-type channels in immune cells and their potential role in shaping the autoimmune response.

Original language	English (US)
Pages (from-to)	782-794
Number of pages	13
Journal	Immunity
Volume	44
Issue number	4
DOIs	https://doi.org/10.1016/j.immuni.2016.01.015
State	Published - Apr 19 2016

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Infectious Diseases

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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.",

author = "Huiyun Wang and Xuexin Zhang and Li Xue and Juan Xing and Jouvin, {Marie H{\'e}l{\`e}ne} and Putney, {James W.} and Anderson, {Matthew P.} and Mohamed Trebak and Kinet, {Jean Pierre}",

note = "Funding Information: This work was funded in part by NIH grants 5T32HL789315 to H.W., HL097111 to M.T., 5R01NS081916 to M.P.A., and 5R37GM53950 and 1R01AI095308 to J.-P.K. ",

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T1 - Low-Voltage-Activated CaV3.1 Calcium Channels Shape T Helper Cell Cytokine Profiles

AU - Wang, Huiyun

AU - Zhang, Xuexin

AU - Xue, Li

AU - Xing, Juan

AU - Jouvin, Marie Hélène

AU - Putney, James W.

AU - Anderson, Matthew P.

AU - Trebak, Mohamed

AU - Kinet, Jean Pierre

N1 - Funding Information: This work was funded in part by NIH grants 5T32HL789315 to H.W., HL097111 to M.T., 5R01NS081916 to M.P.A., and 5R37GM53950 and 1R01AI095308 to J.-P.K.

PY - 2016/4/19

Y1 - 2016/4/19

N2 - 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.

AB - 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.

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