چکیده (انگلیسی):

Background: Interleukin (IL)-23Th17 axis plays an important role in the pathophysiology of asthma and eczema,
however, there are some conflicting data about the effects of this system on allergic airway inflammation.
In the present study, we aim to dissect the spatiotemporal differences in the roles of IL-23 in an
epicutaneously-sensitized asthma model of mice.
Methods: C57BL6 mice were sensitized to ovalbumin (OVA) by patch application on the skin, followed by airway
exposure to aerosolized OVA. During sensitization andor challenge phase, either a specific neutralizing
antibody (Ab) against IL-23 or control IgG was injected intraperitoneally. On days 1 and 8 after the final OVA
exposure, airway inflammation and responsiveness to methacholine, immunoglobulin levels in serum, and cytokine
release from splenocytes were evaluated. Skin Il23a mRNA levels were evaluated with quantitative RTPCR.
Results: Patch application time-dependently increased the expression of Il23a mRNA expression in the skin.
Treatment with the anti-IL-23 Ab during sensitization phase alone significantly reduced the number of eosinophils
in bronchoalveolar lavage fluids and peribronchial spaces after allergen challenge compared with treatment
with control IgG. Anti-IL-23 Ab also reduced serum levels of OVA-specific IgG1. In contrast, treatment with
the anti-IL-23 Ab during the challenge phase alone rather exacerbated airway hyperresponsiveness to methacholine
with little effects on airway eosinophilia or serum IgG1 levels.
Conclusions: IL-23 expressed in the skin during the sensitization phase plays an essential role in the development
of allergic phenotypes, whereas IL-23 in the airways during the challenge phase suppresses airway hyperresponsiveness.