IkB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for Degranulation

Authors
Katrin Peschke, Anke Weitzmann, Klaus Heger, Rayk Behrendt, Nadja Schubert, Julia Scholten, David Voehringer, Karin Hartmann, Anne Dudeck, Marc Schmidt-Supprian and Axel Roers


Lab
Technische Universita¨t Dresden, Medical Faculty Carl Gustav Carus, Dresden, Germany

Journal
Cell Reports

Abstract
The immunoglobulin E (IgE)-mediated mast cell (MC) response is central to the pathogenesis of type I allergy and asthma. IkB kinase 2 (IKK2) was reported to couple IgE-induced signals to MC degranulation by phosphorylating the SNARE protein SNAP23. We investigated MC responses in mice with MC-specific inactivation of IKK2 or NF-kB essential modulator (NEMO), or animals with MC-specific expression of a mutant, constitutively active IKK2. We show that the IgE-induced late-phase cytokine response is reduced in mice lacking IKK2 or NEMO in MCs. However, anaphylactic in vivo responses of these animals are not different from those of control mice, and in vitro IKK2-deficient MCs readily phosphorylate SNAP23 and degranulate similarly to control cells in response to allergen or calcium ionophore. Constitutive overactivation of the NF-kB pathway has only slight effects on allergen-triggered MC responses. Thus, IKK2 is dispensable for MC degranulation, and the important question how IgEinduced signals trigger MC vesicle fusion remains open. 

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