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Nature Immunology 9, 81–88 (1 January 2008) | doi:10.1038/ni1546

Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses

Yoshihiro Baba , Keigo Nishida , Yoko Fujii , Toshio Hirano , Masaki Hikida & Tomohiro Kurosaki

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 Fc|[epsi]|RI and activation of the transcription factors NF-κB and NFAT. Mast cells lacking STIM1 also had much less degranulation and cytokine production after Fc|[epsi]|RI 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 Fc|[epsi]|RI-mediated mast cell activation and anaphylaxis.