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*

*Corresponding author for this work

Research output: Contribution to journalArticle

412 Scopus citations

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 (US)
Pages (from-to)432-443
Number of pages12
JournalNature Immunology
Volume9
Issue number4
DOIs
StatePublished - Apr 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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