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The Bcl10–Malt1 complex segregates FcɛRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation
Mast cells are pivotal effector cells in IgE-mediated allergic inflammatory diseases. Central for mast cell activation are signals from the IgE receptor FcɛRI, which induce cell degranulation with the release of preformed mediators and de novo synthesis of proinflammatory leukotrienes and cytokines....
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118204/ https://www.ncbi.nlm.nih.gov/pubmed/16432253 http://dx.doi.org/10.1084/jem.20051982 |
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author | Klemm, Stefanie Gutermuth, Jan Hültner, Lothar Sparwasser, Tim Behrendt, Heidrun Peschel, Christian Mak, Tak W. Jakob, Thilo Ruland, Jürgen |
author_facet | Klemm, Stefanie Gutermuth, Jan Hültner, Lothar Sparwasser, Tim Behrendt, Heidrun Peschel, Christian Mak, Tak W. Jakob, Thilo Ruland, Jürgen |
author_sort | Klemm, Stefanie |
collection | PubMed |
description | Mast cells are pivotal effector cells in IgE-mediated allergic inflammatory diseases. Central for mast cell activation are signals from the IgE receptor FcɛRI, 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 κB (NF-κB) nor produce tumor necrosis factor α or interleukin 6 upon FcɛRI ligation even though proximal signaling, degranulation, and leukotriene secretion are normal. Thus, Bcl10 and Malt1 are essential positive mediators of FcɛRI-dependent mast cell activation that selectively uncouple NF-κB–induced proinflammatory cytokine production from degranulation and leukotriene synthesis. |
format | Text |
id | pubmed-2118204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21182042007-12-13 The Bcl10–Malt1 complex segregates FcɛRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation Klemm, Stefanie Gutermuth, Jan Hültner, Lothar Sparwasser, Tim Behrendt, Heidrun Peschel, Christian Mak, Tak W. Jakob, Thilo Ruland, Jürgen J Exp Med Articles Mast cells are pivotal effector cells in IgE-mediated allergic inflammatory diseases. Central for mast cell activation are signals from the IgE receptor FcɛRI, 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 κB (NF-κB) nor produce tumor necrosis factor α or interleukin 6 upon FcɛRI ligation even though proximal signaling, degranulation, and leukotriene secretion are normal. Thus, Bcl10 and Malt1 are essential positive mediators of FcɛRI-dependent mast cell activation that selectively uncouple NF-κB–induced proinflammatory cytokine production from degranulation and leukotriene synthesis. The Rockefeller University Press 2006-02-20 /pmc/articles/PMC2118204/ /pubmed/16432253 http://dx.doi.org/10.1084/jem.20051982 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Klemm, Stefanie Gutermuth, Jan Hültner, Lothar Sparwasser, Tim Behrendt, Heidrun Peschel, Christian Mak, Tak W. Jakob, Thilo Ruland, Jürgen The Bcl10–Malt1 complex segregates FcɛRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation |
title | The Bcl10–Malt1 complex segregates FcɛRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation |
title_full | The Bcl10–Malt1 complex segregates FcɛRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation |
title_fullStr | The Bcl10–Malt1 complex segregates FcɛRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation |
title_full_unstemmed | The Bcl10–Malt1 complex segregates FcɛRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation |
title_short | The Bcl10–Malt1 complex segregates FcɛRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation |
title_sort | bcl10–malt1 complex segregates fcɛri-mediated nuclear factor κb activation and cytokine production from mast cell degranulation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118204/ https://www.ncbi.nlm.nih.gov/pubmed/16432253 http://dx.doi.org/10.1084/jem.20051982 |
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