JunB is required for IgE-mediated degranulation and cytokine release of mast cells.
Mast cells are effector cells of IgE-mediated immune responses frequently found at the vicinity of blood vessels, the margins of diverse tumors and at sites of potential infection and inflammation. Upon IgE-mediated stimulation, mast cells produce and secrete a broad spectrum of cytokines and other inflammatory mediators. Recent work identified JunB, a member of the AP-1 transcription factor family, as critical regulator of basal and induced expression of inflammatory mediators in fibroblasts and T cells. To study the impact of JunB on mast cell biology, we analyzed JunB-deficient mast cells. Mast cells lacking JunB display a normal in vivo maturation, and JunB-deficient bone marrow cells in vitro differentiated to mast cells show no alterations in proliferation or apoptosis. But these cells exhibit impaired IgE-mediated degranulation most likely due to diminished expression of SWAP-70, Synaptotagmin-1, and VAMP-8, and due to impaired influx of extracellular calcium. Moreover, JunB-deficient bone marrow mast cells display an altered cytokine expression profile in response to IgE stimulation. In line with these findings, the contribution of JunB-deficient mast cells to angiogenesis, as analyzed in an in vitro tube formation assay on matrigel, is severely impaired due to limiting amounts of synthesized and secreted vascular endothelial growth factor. Thus, JunB is a critical regulator of intrinsic mast cell functions including cross-talk with endothelial cells.
Textor
Björn
B
Deutsches Krebsforschungszentrum Heidelberg, Division of Signal Transduction and Growth Control (A100), Heidelberg, Germany.
Licht
Alexander H
AH
Tuckermann
Jan P
JP
Jessberger
Rolf
R
Razin
Ehud
E
Angel
Peter
P
Schorpp-Kistner
Marina
M
Hartenstein
Bettina
B
D000818:Animals; D002118:Calcium / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D020662:Guanine Nucleotide Exchange Factors / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D007239:Infections / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D015778:Minor Histocompatibility Antigens; D009369:Neoplasms / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology; D016755:Proto-Oncogene Proteins c-jun / Q000172:deficiency / Q000276:immunology*; D050683:R-SNARE Proteins / Q000276:immunology; D050863:Synaptotagmin I / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D018836:Inflammation Mediators; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; D050683:R-SNARE Proteins; C113365:Swap70 protein, mouse; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; D018808:Transcription Factor AP-1; C491831:Vamp8 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D007073:Immunoglobulin E; D002118:Calcium