Airway epithelial NF-κB activation promotes allergic sensitization to an innocuous inhaled antigen

Am J Respir Cell Mol Biol. 2011 May;44(5):631-8. doi: 10.1165/rcmb.2010-0106OC. Epub 2010 Jun 25.


Activation of NF-κB in airway epithelium is observed in allergic asthma and is induced by inhalation of numerous infectious and reactive substances. Many of the substances that activate NF-κB in the airway epithelium are also capable of acting as adjuvants to elicit antigen-specific sensitization to concomitantly inhaled protein, thereby circumventing the inherent bias of the lung to promote tolerance to innocuous antigens. We have used a transgenic mouse inducibly expressing a constitutively active mutant of the inhibitor of nuclear factor κB (IκB) kinase β ((CA)IKKβ) that activates NF-κB only in nonciliated airway epithelial cells to test whether activation of this intracellular signaling pathway in this specific cell type is sufficient to establish a pulmonary environment permissive to the development of allergic sensitization to inhaled protein. When airway epithelial (CA)IKKβ was transiently expressed in antigen-naive mice only during initial inhalation of ovalbumin, the mice became allergically sensitized to the antigen. As a consequence, subsequent inhalation of ovalbumin alone led to an allergic asthma-like response that included airway hyperresponsiveness to methacholine, eosinophilia, mucus expression, elevated serum levels of antigen-specific IgE and IgG1, and splenic CD4(+) T cells that secreted T helper type 2 and type 17 cytokines in response to in vitro antigen restimulation. Furthermore, CD11c(+) cells in the mediastinal lymph nodes (MLN) of (CA)IKKβ-expressing mice displayed significantly elevated levels of activation markers. These data implicate airway epithelial NF-κB activation as a critical modulator of the adaptive immune response to inhaled antigens via the secretion of soluble mediators that affect the capacity of CD11c(+) cells to undergo maturation and promote antigen-specific allergic responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen-Presenting Cells / cytology
  • Asthma / immunology
  • Bronchi / metabolism*
  • Bronchoalveolar Lavage
  • CD11c Antigen / biosynthesis
  • CD4-Positive T-Lymphocytes / cytology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Female
  • Hypersensitivity / immunology*
  • Inhalation
  • Lung / immunology
  • Lung / pathology
  • Lymph Nodes / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • NF-kappa B / metabolism*
  • Signal Transduction


  • CD11c Antigen
  • NF-kappa B