New IL-17 Family Members Promote Th1 or Th2 Responses in the Lung: In Vivo Function of the Novel Cytokine IL-25

摘要: We have biologically characterized two new members of the IL-17 cytokine family: IL-17F and IL-25. In contrast to conventional in vitro screening approaches, we activity these molecules by direct vivo analysis compared their function that other family members. Intranasal administration adenovirus expressing IL-17, IL-17C, or resulted bronchoalveolar lavage neutrophilia inflammatory gene expression lung. contrast, intranasal IL-25-expressing IL-25 protein production IL-4, IL-5, IL-13, eotaxin mRNA lung marked eosinophilia tissue. Mice given also developed epithelial cell hyperplasia, increased mucus secretion, airway hyperreactivity. was detected following Aspergillus Nippostrongylus infection gut, respectively. IL-25-induced required IL-5 but not IL-4 T cells. Following administration, IL-5(+) staining cells were CD45R/B220(+), Thy-1(+/-), NK1.1-, Ly-6G(GR-1)-, CD4-, CD3-, c-kit-negative. gamma-common knockout mice did develop response IL-25, nor detected. These findings suggest existence a previously unrecognized population may initiate Th2-like responses responding vivo. Further, data demonstrate heterogeneity within be an important mediator allergic disease via eotaxin.