Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance

Masatsugu Oh-hora, Megumi Yamashita, Patrick G. Hogan, Sonia Sharma, Ed Lamperti, Woo Chung, Murali Prakriya, Stefan Feske, Anjana Rao

    Research output: Contribution to journalArticlepeer-review

    416 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)432-443
    Number of pages12
    JournalNature Immunology
    Volume9
    Issue number4
    DOIs
    Publication statusPublished - Apr 2008

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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