Immune Modulation of the T Cell Response in Asthma through Wnt10b

• Published in: American journal of respiratory cell and molecular biology Vol. 54; no. 4; pp. 584 - 593
• Main Authors: Trischler, Jordis, Shiomi, Takayuki, Turner, Damian L, Sklepkiewicz, Piotr L, Goldklang, Monica P, Tanaka, Kenji F, Xu, Ming, Farber, Donna L, D'Armiento, Jeanine M
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.04.2016
• Subjects: Allergies; Animals; Antigens; Asthma; Asthma - immunology; Bronchoalveolar Lavage Fluid; Cell Polarity; Dermatophagoides pteronyssinus; Disease; Disease Models, Animal; Laboratories; Ligands; Lung - immunology; Lungs; Lymphocytes; Mice; Mice, Knockout; Original Research; Pathogenesis; Rodents; Spleen - immunology; Spleen - pathology; Stem cells; Studies; T cell receptors; T-Lymphocytes - immunology; Transcription factors; Wnt Proteins - genetics; Wnt Proteins - physiology; T helper type 2; allergy; asthma; Wnt pathway; Wnt10b
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2014-0425OC

Asthma is a chronic inflammatory disease, which is characterized by activation of CD4(+) T helper 2 cells orchestrating an allergic airway response. Whereas the role of Wnt family members in regulating T cell maintenance and maturation is established, their contribution to T cell activation in allergic asthma is not known. We hypothesized that Wnt10b plays a role in the modulation of the allergic airway response and affects T cell activation and polarization. Using an in vivo house dust mite asthma model, Wnt10b-deficient (Wnt10b(-/-)) mice were allergen-sensitized and inflammation, as well as T cell activation, was studied in vivo and in vitro. Wnt10b(-/-) mice exhibited an augmented inflammatory phenotype with an increase in eosinophils in the bronchoalveolar lavage and IL-4 and IL-13 in the lungs when compared with wild-type mice. In vitro studies confirmed an increased T helper type 2 polarization and increased T cell activation of Wnt10b(-/-) cells. Accordingly, the percentage of naive T cells was elevated by the addition of recombinant Wnt10b protein. Finally, Wnt10b(-/-) mice exhibited an increase in the percentage of effector T cells in the lungs after house dust mite sensitization, which indicated a heightened activation state, measured by an increased percentage of CD69(hi)CD11a(hi) cells. These findings suggest that Wnt10b plays an important role in regulating asthmatic airway inflammation through modification of the T cell response and is a prospective target in the disease process.