B7-DC Regulates Asthmatic Response by an IFN-γ-Dependent Mechanism

Koichiro Matsumoto, Hiromasa Inoue, Takako Nakano, Miyuki Tsuda, Yuki Yoshiura, Satoru Fukuyama, Fumihiko Tsushima, Tomoaki Hoshino, Hisamichi Aizawa, Hisaya Akiba, Drew Pardoll, Nobuyuki Hara, Hideo Yagita, Miyuki Azuma, Yoichi Nakanishi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2530-2541
Number of pages12
JournalJournal of Immunology
Volume172
Issue number4
DOIs
StatePublished - Feb 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Matsumoto, K., Inoue, H., Nakano, T., Tsuda, M., Yoshiura, Y., Fukuyama, S., Tsushima, F., Hoshino, T., Aizawa, H., Akiba, H., Pardoll, D., Hara, N., Yagita, H., Azuma, M., & Nakanishi, Y. (2004). B7-DC Regulates Asthmatic Response by an IFN-γ-Dependent Mechanism. Journal of Immunology, 172(4), 2530-2541. https://doi.org/10.4049/jimmunol.172.4.2530