B7-DC induced by IL-13 works as a feedback regulator in the effector phase of allergic asthma

IL-13 诱导的 B7-DC 在过敏性哮喘的效应阶段起反馈调节作用

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作者:Koichiro Matsumoto, Satoru Fukuyama, Miyuki Eguchi-Tsuda, Takako Nakano, Takafumi Matsumoto, Mikiko Matsumura, Atsushi Moriwaki, Keiko Kan-o, Yoshihiro Wada, Hideo Yagita, Tahiro Shin, Drew M Pardoll, Rirprajak Patcharee, Miyuki Azuma, Yoichi Nakanishi, Hiromasa Inoue

Abstract

B7-DC is a costimulatory molecule belonging to the B7 family. We previously found that treatment with anti-B7-DC mAb during the effector phase enhances asthma phenotypes in mice. We investigated the mechanisms of B7-DC induction and how B7-DC regulates asthma phenotypes. In allergen-challenged IFN-gamma-deficient mice, anti-B7-DC mAb failed to enhance the asthma phenotypes although the induction of B7-DC on dendritic cells of the mice was comparable with that on dendritic cells of wild-type mice. B7-DC on dendritic cells was up-regulated by IL-13 in vitro. The induction of B7-DC on dendritic cells after allergen challenge was attenuated by blockade of IL-13 in vivo. The asthma phenotypes were enhanced in B7-DC-deficient mice, more than in wild-type mice. The enhancement was concurrent with the down-regulation of IFN-gamma and up-regulation of IL-13. These results suggest that B7-DC induced by IL-13 works as a feedback regulator by up-regulating IFN-gamma production during the effector phase of allergic asthma.

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