Abstract
Store-operated Ca2+ entry through calcium release-activated calcium channels is the chief mechanism for increasing intracellular Ca2+ in immune cells. Here we show that mouse T cells and fibroblasts lacking the calcium sensor STIM1 had severely impaired store-operated Ca2+ influx, whereas deficiency in the calcium sensor STIM2 had a smaller effect. However, T cells lacking either STIM1 or STIM2 had much less cytokine production and nuclear translocation of the transcription factor NFAT. T cell-specific ablation of both STIM1 and STIM2 resulted in a notable lymphoproliferative phenotype and a selective decrease in regulatory T cell numbers. We conclude that both STIM1 and STIM2 promote store-operated Ca2+ entry into T cells and fibroblasts and that STIM proteins are required for the development and function of regulatory T cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Biological Transport, Active / genetics
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Biological Transport, Active / immunology
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Calcium / metabolism
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Calcium Channels
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Cell Line
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Cell Line, Transformed
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Cells, Cultured
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Endoplasmic Reticulum / metabolism*
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Endoplasmic Reticulum / physiology
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Humans
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Immune Tolerance* / genetics
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Molecular Sequence Data
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Stromal Interaction Molecule 1
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Stromal Interaction Molecule 2
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T-Lymphocytes, Regulatory / immunology*
Substances
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Calcium Channels
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Membrane Glycoproteins
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Stim1 protein, mouse
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Stim2 protein, mouse
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Stromal Interaction Molecule 1
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Stromal Interaction Molecule 2
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Calcium