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PMID:16432253

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Citation

Klemm, S, Gutermuth, J, Hültner, L, Sparwasser, T, Behrendt, H, Peschel, C, Mak, TW, Jakob, T and Ruland, J (2006) The Bcl10-Malt1 complex segregates Fc epsilon RI-mediated nuclear factor kappa B activation and cytokine production from mast cell degranulation. J. Exp. Med. 203:337-47

Abstract

Mast cells are pivotal effector cells in IgE-mediated allergic inflammatory diseases. Central for mast cell activation are signals from the IgE receptor FcepsilonRI, which induce cell degranulation with the release of preformed mediators and de novo synthesis of proinflammatory leukotrienes and cytokines. How these individual mast cell responses are differentially controlled is still unresolved. We identify B cell lymphoma 10 (Bcl10) and mucosa-associated lymphoid tissue 1 (Malt1) as novel key regulators of mast cell signaling. Mice deficient for either protein display severely impaired IgE-dependent late phase anaphylactic reactions. Mast cells from these animals neither activate nuclear factor kappaB (NF-kappaB) nor produce tumor necrosis factor alpha or interleukin 6 upon FcepsilonRI ligation even though proximal signaling, degranulation, and leukotriene secretion are normal. Thus, Bcl10 and Malt1 are essential positive mediators of FcepsilonRI-dependent mast cell activation that selectively uncouple NF-kappaB-induced proinflammatory cytokine production from degranulation and leukotriene synthesis.

Links

PubMed PMC2118204 Online version:10.1084/jem.20051982

Keywords

Adaptor Proteins, Signal Transducing/deficiency; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/physiology; Animals; Caspases; Cell Degranulation/immunology; Cells, Cultured; Cytokines/biosynthesis; Immunoglobulin E/physiology; Lipid Metabolism/genetics; Lipid Metabolism/immunology; Lymphoma, B-Cell, Marginal Zone/genetics; Mast Cells/immunology; Mast Cells/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Multiprotein Complexes/deficiency; Multiprotein Complexes/genetics; Multiprotein Complexes/physiology; NF-kappa B/metabolism; Neoplasm Proteins/deficiency; Neoplasm Proteins/genetics; Neoplasm Proteins/physiology; Receptors, IgE/physiology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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