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The Bcl10–Malt1 complex segregates FcεRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation

2006; Rockefeller University Press; Volume: 172; Issue: 4 Linguagem: Inglês

10.1083/jcb1724oia7

1540-8140

Stefanie Klemm, Jan Gutermuth, Lothar Hültner, Tim Sparwasser, Heidrun Behrendt, Christian Peschel, Tak W. Mak, Thilo Jakob, Jürgen Ruland,

PI3K/AKT/mTOR signaling in cancer

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