TY - JOUR
T1 - B7-DC Regulates Asthmatic Response by an IFN-γ-Dependent Mechanism
AU - Matsumoto, Koichiro
AU - Inoue, Hiromasa
AU - Nakano, Takako
AU - Tsuda, Miyuki
AU - Yoshiura, Yuki
AU - Fukuyama, Satoru
AU - Tsushima, Fumihiko
AU - Hoshino, Tomoaki
AU - Aizawa, Hisamichi
AU - Akiba, Hisaya
AU - Pardoll, Drew
AU - Hara, Nobuyuki
AU - Yagita, Hideo
AU - Azuma, Miyuki
AU - Nakanishi, Yoichi
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2004/2/15
Y1 - 2004/2/15
N2 - B7-H1 (PD-L1) and B7-DC (PD-L2) are the ligands for programmed death-1 (PD-1), which is a member of the CD28/CTLA-4 family and has been implicated in peripheral tolerance. We investigated the roles of B7-H1 and B7-DC in a murine OVA-induced allergic asthma model. B7-H1 was constitutively expressed on dendritic cells, macrophages, B cells, and T cells in the lungs of naive mice, and its expression could be dramatically increased after allergen challenge. In contrast, B7-DC expression was scarcely expressed on dendritic cells in naive mice, but was up-regulated after allergen challenge, although the up-regulation of B7-DC expression on macrophages was minimal. Treatment of mice with anti-B7-DC mAb at the time of allergen challenge, but not at the time of sensitization, significantly increased their airway hyper-reactivity and eosinophilia. Such treatment also resulted in the increased production of IL-5 and IL-13, and decreased IFN-γ production in the lungs and draining lymph node cells. These changes were diminished when mice were depleted of IFN-γ by anti-IFN-γ mAb pretreatment. Interestingly, treatment with anti-B7-H1 or anti-PD-1 mAb did not significantly affect the asthmatic response. These results suggest a unique role for B7-DC in the regulation of asthmatic response through an IFN-γ-dependent, but PD-1-independent, mechanism.
AB - B7-H1 (PD-L1) and B7-DC (PD-L2) are the ligands for programmed death-1 (PD-1), which is a member of the CD28/CTLA-4 family and has been implicated in peripheral tolerance. We investigated the roles of B7-H1 and B7-DC in a murine OVA-induced allergic asthma model. B7-H1 was constitutively expressed on dendritic cells, macrophages, B cells, and T cells in the lungs of naive mice, and its expression could be dramatically increased after allergen challenge. In contrast, B7-DC expression was scarcely expressed on dendritic cells in naive mice, but was up-regulated after allergen challenge, although the up-regulation of B7-DC expression on macrophages was minimal. Treatment of mice with anti-B7-DC mAb at the time of allergen challenge, but not at the time of sensitization, significantly increased their airway hyper-reactivity and eosinophilia. Such treatment also resulted in the increased production of IL-5 and IL-13, and decreased IFN-γ production in the lungs and draining lymph node cells. These changes were diminished when mice were depleted of IFN-γ by anti-IFN-γ mAb pretreatment. Interestingly, treatment with anti-B7-H1 or anti-PD-1 mAb did not significantly affect the asthmatic response. These results suggest a unique role for B7-DC in the regulation of asthmatic response through an IFN-γ-dependent, but PD-1-independent, mechanism.
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U2 - 10.4049/jimmunol.172.4.2530
DO - 10.4049/jimmunol.172.4.2530
M3 - Article
C2 - 14764726
AN - SCOPUS:10744226932
SN - 0022-1767
VL - 172
SP - 2530
EP - 2541
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -