Activation of the β-catenin pathway by Wnt-1 treatment suppress inflammation in the mouse model of allergic airway disease

Abstract

Introduction: Current observations reveal an anti-inflammatory effect of Wnt mediated β-catenin signaling during allergic airway disease. Indeed, lung specific overexpression of Wnt-1 attenuates experimental allergic airway disease (Reuter, S. et al. J Immunol 2014;193:485-95). The aim of the following study was to investigate the effect of recurrent Wnt-1 exposure in a therapeutic fashion in a murine model of allergic airway disease. Method: After the intraperitoneal sensitization with Ovalbumin(OVA)/Aluminium hydroxide on days 0 and 14, C57BL/6 mice were challenged via the airways by nebulization of a 1% OVA solution on days 28-30. Some animals received recombinant Wnt-1 intranasal one hour prior to each challenge. 48 hours after the last challenge the allergic airway disease was analyzed. Results: The application of Wnt-1 significant diminishes airway hyper responsiveness, goblet cell metaplasia and lung inflammation. Moreover, Wnt-1 treated animals demonstrated a reduced Interleukin (IL)-13 secretion of ex vivo lung and draining lymph node cells. Furthermore, the pattern of cDC (conventional dendritic cells) subpopulation in the lung differed between treated and untreated animals. Sensitized animals without Wnt-1 treatment demonstrated a CD11b dominated ratio of cDC in the lung whereas Wnt-1 treated animals revealed a balanced ratio of CD11b to CD103 positive cDC. The frequency of regulatory T cells or the secretion of IL-10 was unaffected. Conclusion: These data demonstrate the suppression of allergic airway disease by activating the canonical Wnt/β-catenin-pathway using Wnt-1 ligand.