IκB kinase 2 is essential for IgE-induced mast cell de novo cytokine production but not for degranulation

Cell Rep. 2014 Sep 11;8(5):1300-7. doi: 10.1016/j.celrep.2014.07.046. Epub 2014 Aug 28.


The immunoglobulin E (IgE)-mediated mast cell (MC) response is central to the pathogenesis of type I allergy and asthma. IκB 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-κB 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-κB pathway has only slight effects on allergen-triggered MC responses. Thus, IKK2 is dispensable for MC degranulation, and the important question how IgE-induced signals trigger MC vesicle fusion remains open.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Anaphylaxis / metabolism
  • Animals
  • Cell Degranulation*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • Immunoglobulin E / immunology*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mast Cells / immunology
  • Mast Cells / metabolism*
  • Mast Cells / physiology
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Qb-SNARE Proteins / metabolism
  • Qc-SNARE Proteins / metabolism


  • Allergens
  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • NEMO protein, mouse
  • NF-kappa B
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • Snap23 protein, mouse
  • Immunoglobulin E
  • I-kappa B Kinase
  • Ikbkb protein, mouse