Article abstract
Nature Immunology 9, 81 - 88 (2008)
Published online: 2 December 2007 | doi:10.1038/ni1546
Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses
Yoshihiro Baba1, Keigo Nishida2, Yoko Fujii1, Toshio Hirano2, Masaki Hikida1 & Tomohiro Kurosaki1
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 Fc
RI and activation of the transcription factors NF-
B and NFAT. Mast cells lacking STIM1 also had much less degranulation and cytokine production after FcRI 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 FcRI-mediated mast cell activation and anaphylaxis.
- Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
- Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Correspondence to: Tomohiro Kurosaki1 e-mail: kurosaki@rcai.riken.jp
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