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

Nature Immunology volume 9, pages 81–88 (2008)Cite this article

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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Figure 1: Development of Stim1−/− mast cells.
Figure 2: Suppression of SOC influx in Stim1−/− FLMCs.
Figure 3: STIM1 is required for FcεRI-induced degranulation and cytokine production.
Figure 4: FcεRI-proximal signaling and activation of MAP kinases in Stim1+/+ and Stim1−/− FLMCs.
Figure 5: Activation of NF-κB and NFAT is inhibited in Stim1−/− FLMCs.
Figure 6: In vivo anaphylaxis is lower in Stim1+/− mice.

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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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Authors and Affiliations

  1. Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehirocho, Tsurumi-ku, Yokohama, 230-0045, Kanagawa, Japan

    Yoshihiro Baba, Yoko Fujii, Masaki Hikida & Tomohiro Kurosaki

  2. Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehirocho, Tsurumi-ku, Yokohama, 230-0045, Kanagawa, Japan

    Keigo Nishida & Toshio Hirano

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  1. Yoshihiro Baba
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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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Correspondence to Tomohiro Kurosaki.

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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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