| Author |
Taube, Christian Belz, Christina Stassen, Michael Buhl, Roland Montermann, Evelyn Reuter, Sebastian Sahin, Ugur Eshkind, Leonid Martin, Helen Ohngemach, Svetlana Beckert, Hendrik Bros, Matthias Heinz, Anke |
| Description |
Author Affiliation: Reuter S ( Pulmonary Department, III. Medical Clinic, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Martin H ( Pulmonary Department, III. Medical Clinic, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Beckert H ( Pulmonary Department, III. Medical Clinic, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Bros M ( Department of Dermatology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Montermann E ( Department of Dermatology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Belz C ( Pulmonary Department, III. Medical Clinic, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Heinz A ( Pulmonary Department, III. Medical Clinic, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Ohngemach S ( Transgenic Facility, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Sahin U ( III. Medical Clinic, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Stassen M ( Institute of Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Buhl R ( Pulmonary Department, III. Medical Clinic, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Eshkind L ( Transgenic Facility, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany); Taube C ( Department of Pulmonology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands C.Taube@lumc.nl sebastian.reuter@unimedizin-mainz.de.) |
| Abstract |
Signaling via the Wnt/ß-catenin pathway plays crucial roles in embryogenesis and homeostasis of adult tissues. In the lung, the canonical Wnt/ß-catenin pathway has been implicated in remodeling processes, development of emphysema, and fibrosis. However, its relevance for the modulation of allergic responses in the lung remains unclear. Using genetically modified mice with lung-specific inducible (doxycycline) Wnt-1 expression (CCSP-rtTA × tetO-Wnt1), the impact of Wnt on the development of allergic airway disease was analyzed. Overexpression of Wnt during the allergen challenge phase attenuated the development of airway inflammation in an acute model, as well as in a more therapeutic model of secondary challenge. These findings were further supported by treatment of allergen-sensitized mice with LiCl during challenge. Similar to Wnt, LiCl prevented the degradation of ß-catenin and, thus, attenuated allergic airway inflammation and hyperresponsiveness. Migration studies revealed that lung-specific expression of Wnt reduced the migration of Ag-loaded dendritic cells (DCs) into the draining lymph nodes following allergen challenge. Administration of in vitro allergen-loaded DCs overcame Wnt-mediated suppression of airway inflammation. Furthermore, in vitro studies confirmed that DC-dependent T cell activation is impaired by blocking ß-catenin degradation. These results demonstrate an important role for the canonical Wnt/ß-catenin pathway in the DC-mediated regulation of allergic responses in the lung. |
