Article abstract
Nature Immunology 9, 432 - 443 (2008)
Published online: 9 March 2008 | doi:10.1038/ni1574
Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance
Masatsugu Oh-hora1, Megumi Yamashita2, Patrick G Hogan1, Sonia Sharma1, Ed Lamperti1, Woo Chung2, Murali Prakriya2, Stefan Feske1,3 & Anjana Rao1
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.
- Harvard Medical School and Immune Disease Institute, Boston, Massachusetts 02115, USA.
- Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA.
- Present address: Department of Pathology, New York University, School of Medicine, New York, New York 10016, USA.
Correspondence to: Anjana Rao1 e-mail: arao@cbr.med.harvard.edu
Correspondence to: Stefan Feske1,3 e-mail: stefan.feske@med.nyu.edu
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