NF-κB Activation by FcεRI-Mediated Signal Transduction

NF-κB is a master transcription factor in immunity and inflammation. It can be activated by a large variety of distinct cell surface receptors in response to multiple stimuli. NF-κB activation by the high affinity IgE receptor FcεRI is critical for proinflammatory cytokine production during mast cell activation and is crucial for allergic inflammatory diseases. Recent studies have identified two adaptor proteins, Bcl10 and Malt1, as essential regulators of FcεRI-mediated NF-κB activation. Bcl10 and Malt1 form a signaling complex that operates downstream of PKC enzymes and regulates the production of proinflammatory cytokines in response to FcεRI signaling. Other PKC-dependent mast cell effector functions like degranulation or leukotriene production are not controlled by Bcl10 and Malt1. Thus, the Bcl10/Malt1 complex specifically uncouples the pathway for transcription-dependent cytokine production from degranulation events. This review will summarize our current knowledge of the specific NF-κB activation pathway that is selectively engaged by FcεRI ligation in mast cells.