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 F. Tanaka, Ming Xu, Donna L. Farber, Jeanine M. D'Armiento

研究成果: Article査読

19 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)584-593
ページ数10
ジャーナルAmerican journal of respiratory cell and molecular biology
54
4
DOI
出版ステータスPublished - 2016 4月

ASJC Scopus subject areas

  • 分子生物学
  • 呼吸器内科
  • 臨床生化学
  • 細胞生物学

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