| First Author | Ather JL | Year | 2011 |
| Journal | Am J Respir Cell Mol Biol | Volume | 44 |
| Issue | 5 | Pages | 631-8 |
| PubMed ID | 20581095 | Mgi Jnum | J:185033 |
| Mgi Id | MGI:5427082 | Doi | 10.1165/rcmb.2010-0106OC |
| Citation | Ather JL, et al. (2011) Airway epithelial NF-kappaB activation promotes allergic sensitization to an innocuous inhaled antigen. Am J Respir Cell Mol Biol 44(5):631-8 |
| abstractText | Activation of NF-kappaB 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-kappaB 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 kappaB (IkappaB) kinase beta ((CA)IKKbeta) that activates NF-kappaB 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)IKKbeta 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)IKKbeta-expressing mice displayed significantly elevated levels of activation markers. These data implicate airway epithelial NF-kappaB 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. |
