Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses.
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 FcepsilonRI and activation of the transcription factors NF-kappaB and NFAT. Mast cells lacking STIM1 also had much less degranulation and cytokine production after FcepsilonRI 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 FcepsilonRI-mediated mast cell activation and anaphylaxis.
Baba
Yoshihiro
Y
Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Nishida
Keigo
K
Fujii
Yoko
Y
Hirano
Toshio
T
Hikida
Masaki
M
Kurosaki
Tomohiro
T
D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D015550:Cell Degranulation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007073:Immunoglobulin E / Q000502:physiology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology; D000071737:Stromal Interaction Molecule 1; D013601:T-Lymphocytes / Q000276:immunology
D015220:Calcium Channels; D016207:Cytokines; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D017455:Receptors, IgE; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D007073:Immunoglobulin E; D002118:Calcium