Immune modulation of the T-cell response in asthma through Wnt10b

Rationale : Wnt molecules are critical during development and regulate T-cell maintenance and activation. Utilizing a house dust mite asthma model, this study examined the role of Wnt10b on the asthmatic immune response. Methods: Wnt10b knockout and littermate control mice were i.n. administered HDM extract for 3 weeks. BAL was performed with differential cell counts obtained. Portions of the lung were fixed in formalin or homogenized for ELISA analysis (IL-4, IL-5, IL-13 and IL-17). Lung and lymphoid tissues from HDM sensitized mice were harvested for FACS analysis. Thy1.2-enriched splenic cells were utilized for in vitro proliferation, activation and expression studies after CD3/CD28 treatment. Results: The loss of Wnt10b led to an increase in total cells and eosinophils in the BAL with a 50% increase in IL-13 expression compared to wild-type mice. Furthermore, Wnt10b-deficient BAL cells exhibited increased MCP-1 and Arg-1 expression. Examination of inflammatory cell regulation in vivo revealed increased activation of CD4-positive cells in the Wnt10b KO, HDM-sensitized lung by an increased percentage of CD62L lo CD44 hi cells. A CFSE dilution assay showed increased proliferation of CD4- and CD8-positive cells, which was reversed by the addition of recombinant Wnt10b protein. Wnt10b-deficient, Thy1.2-enriched splenic T-cells exhibited increased GATA3 expression after Th2 polarization compared to the wild-type cells. Conclusion : In the present study Wnt10b-deficiency results in an increase in the Th2-driven inflammatory response in HDM-triggered asthma likely due to increased T-cell activation and Th2 polarization. The findings suggest that Wnt10b plays a role in regulating asthmatic airway inflammation.