The Canonical but Not the Noncanonical Wnt Pathway Inhibits the Development of Allergic Airway Disease

Abstract

Asthma is a syndrome with multifactorial causes, resulting in a variety of different phenotypes. Current treatment options are not curative and are sometimes ineffective in certain disease phenotypes. Therefore, novel therapeutic approaches are required. Recent findings have shown that activation of the canonical Wnt signaling pathway suppresses the development of allergic airway disease. In contrast, the effect of the noncanonical Wnt signaling pathway activation on allergic airway disease is not well described. The aim of this study was to validate the therapeutic effectiveness of Wnt-1–driven canonical Wnt signaling compared with Wnt-5a–driven noncanonical signaling in murine models. In vitro, both ligands were capable of attenuating allergen-specific T cell activation in a dendritic cell–dependent manner. In addition, the therapeutic effects of Wnt ligands were assessed in two different models of allergic airway disease. Application of Wnt-1 resulted in suppression of airway inflammation as well as airway hyperresponsiveness and mucus production. In contrast, administration of Wnt-5a was less effective in reducing airway inflammation or goblet cell metaplasia. These results suggest an immune modulating function for canonical as well as noncanonical Wnt signaling, but canonical Wnt pathway activation appears to be more effective in suppressing allergic airway disease than noncanonical Wnt activation.