Immune modulation of the T cell response in asthma through Wnt10b

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 ofWnt 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 affectsTcell 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 ofWnt10b^-/- cells. Accordingly, the percentage of naive T cells was elevated by the addition of recombinantWnt10b 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^hiCD11a^hi cells. These findings suggest thatWnt10b 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.