Abstract
Mast cells have key functions as effectors of immunoglobulin E–mediated allergic inflammatory diseases. Allergen stimulation induces Ca2+ influx and elicits the secretion of inflammatory mediators from mast cells. Here we show that the Ca2+-binding endoplasmic reticulum protein STIM1 is critical to mast cell function. STIM1-deficient fetal liver–derived mast cells had impaired Ca2+ influx mediated by the high-affinity immunoglobulin E receptor FcεRI and activation of the transcription factors NF-κB and NFAT. Mast cells lacking STIM1 also had much less degranulation and cytokine production after FcεRI stimulation. In addition, alterations in STIM1 expression affected the sensitivity of immunoglobulin E–mediated immediate-phase anaphylactic responses in vivo. Thus, STIM1 is key in promoting the Ca2+ influx that is essential for FcεRI-mediated mast cell activation and anaphylaxis.
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Acknowledgements
We thank A. Ito for technical assistance; P.W. Kincade for critical review of the manuscript; and S. Yamasaki and H. Shinohara for discussions. The pMX-puro retroviral vector was from T. Kitamura (University of Tokyo). Supported the Ministry of Education, Culture, Sports, Science and Technology of Japan (Y.B. and T.K.).
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Y.B. designed and coordinated the study, did experiments, analyzed data and wrote the paper; K.N., Y.F. and M.H. cooperated in experiments; T.K. wrote the paper; and T.H. contributed to manuscript writing.
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Baba, Y., Nishida, K., Fujii, Y. et al. Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses. Nat Immunol 9, 81–88 (2008). https://doi.org/10.1038/ni1546
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DOI: https://doi.org/10.1038/ni1546
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