The Wnt/β-catenin pathway attenuates experimental allergic airway disease.

Abstract

Signaling via the Wnt/β-catenin pathway plays crucial roles in embryogenesis and homeostasis of adult tissues. In the lung, the canonical Wnt/β-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 β-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 β-catenin degradation. These results demonstrate an important role for the canonical Wnt/β-catenin pathway in the DC-mediated regulation of allergic responses in the lung.

• Authors: Sebastian Reuter, Helen Martin, Hendrik Beckert, Matthias Bros, Evelyn Montermann, Christina Belz, Anke Heinz, Svetlana Ohngemach, Ugur Sahin, Michael Stassen, Roland Buhl, Leonid Eshkind, Christian Taube
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 2 Pg. 485-95 (Jul 15 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 24929002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• Adjuvants, Immunologic
• Cytokines
• Wnt1 Protein
• beta Catenin
• Ovalbumin
• Lithium Chloride
• Doxycycline

Topics

• Adjuvants, Immunologic (pharmacology)
• Animals
• Cell Movement (genetics, immunology)
• Cells, Cultured
• Coculture Techniques
• Cytokines (immunology, metabolism)
• Dendritic Cells (immunology, metabolism)
• Doxycycline (pharmacology)
• Flow Cytometry
• Lithium Chloride (immunology, pharmacology)
• Lung (drug effects, metabolism, physiopathology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Transgenic
• Ovalbumin (immunology, pharmacology)
• Respiratory Hypersensitivity (genetics, immunology, prevention & control)
• Signal Transduction (genetics, immunology)
• T-Lymphocytes (immunology, metabolism)
• Wnt1 Protein (genetics, immunology, metabolism)
• beta Catenin (immunology, metabolism)