B7-DC induced by IL-13 works as a feedback regulator in the effector phase of allergic asthma.
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.
Matsumoto
Koichiro
K
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Fukuyama
Satoru
S
Eguchi-Tsuda
Miyuki
M
Nakano
Takako
T
Matsumoto
Takafumi
T
Matsumura
Mikiko
M
Moriwaki
Atsushi
A
Kan-o
Keiko
K
Wada
Yoshihiro
Y
Yagita
Hideo
H
Shin
Tahiro
T
Pardoll
Drew M
DM
Patcharee
Rirprajak
R
Azuma
Miyuki
M
Nakanishi
Yoichi
Y
Inoue
Hiromasa
H
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D015536:Down-Regulation; D025461:Feedback, Physiological; D006967:Hypersensitivity / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018793:Interleukin-13 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010641:Phenotype; D061027:Programmed Cell Death 1 Ligand 2 Protein; D015854:Up-Regulation
D018122:B7-1 Antigen; D018793:Interleukin-13; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D007371:Interferon-gamma