Airway Epithelial NF-kappa B Activation Promotes Allergic Sensitization to an Innocuous Inhaled Antigen

作者：Ather Jennifer L; Hodgkins Samantha R; Janssen Heininger Yvonne M W; Poynter Matthew E^*

来源：American Journal of Respiratory Cell and Molecular Biology, 2011, 44(5): 631-638.

DOI：10.1165/rcmb.2010-0106OC

• epithelial cell
• antigen-presenting cell
• NF-kappa B
• allergy
• asthma

Activation of NF-kappa B 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-kB 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 kappa B (I kappa B) kinase beta ((CA)IKK beta) that activates NF-kappa B 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 CAIKKb 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)IKK beta-expressing mice displayed significantly elevated levels of activation markers. These data implicate airway epithelial NF-kappa B 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.

• 出版日期2011-5