Immune modulation of the T cell response in asthma through Wnt10b

Jordis Trischler, Takayuki Shiomi, Damian L. Turner, Piotr L. Sklepkiewicz, Monica P. Goldklang, Kenji Tanaka, Ming Xu, Donna L. Farber, Jeanine M. D'Armiento

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

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 CD69hiCD11ahi 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.

Original languageEnglish
Pages (from-to)584-593
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume54
Issue number4
DOIs
Publication statusPublished - 2016 Apr 1

Keywords

  • Allergy
  • Asthma
  • T helper type 2
  • Wnt pathway
  • Wnt10b

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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