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

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259 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)81-88
Number of pages8
JournalNature Immunology
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 1 2008
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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