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

• Published in: Nature immunology Vol. 9; no. 1; pp. 81 - 88
• Main Authors: Kurosaki, Tomohiro, Baba, Yoshihiro, Nishida, Keigo, Fujii, Yoko, Hirano, Toshio, Hikida, Masaki
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2008; Nature Publishing Group
• Subjects: Allergens; Anaphylaxis; Anaphylaxis - immunology; Animals; Biomedical and Life Sciences; Biomedicine; Calcium - metabolism; Calcium Channels; Causes of; Cell Degranulation; Cells, Cultured; Cytokines - biosynthesis; Development and progression; Endoplasmic Reticulum - metabolism; Health aspects; Immunoglobulin E; Immunoglobulin E - physiology; Immunology; Infectious Diseases; Inflammation; Mast Cells - immunology; Mast Cells - metabolism; Mediators; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Mice, Knockout; NF-kappa B - metabolism; NFATC Transcription Factors - metabolism; Physiological aspects; Receptors, IgE - immunology; Stromal Interaction Molecule 1; T-Lymphocytes - immunology; Japan
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni1546

Mast cells have key functions as effectors of immunoglobulin E–mediated allergic inflammatory diseases. Allergen stimulation induces Ca 2+ influx and elicits the secretion of inflammatory mediators from mast cells. Here we show that the Ca 2+ -binding endoplasmic reticulum protein STIM1 is critical to mast cell function. STIM1-deficient fetal liver–derived mast cells had impaired Ca 2+ 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 Ca 2+ influx that is essential for FcεRI-mediated mast cell activation and anaphylaxis.