HMGB1 blockade significantly improves luminal fibrous obliteration in a murine model of bronchiolitis obliterans syndrome

Shinkichi Takamori, Fumihiro Shoji, Tatsuro Okamoto, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Masakazu Katsura, Kazuki Takada, Gouji Toyokawa, Tetsuzo Tagawa, Yoshihiko Maehara

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Background: Although high-mobility group box-1 (HMGB1), which is a nuclear protein, was reported to enhance the allogeneic responses in transplantation, the effect of HMGB1 on bronchiolitis obliterans syndrome (BOS) is unknown. Methods: A murine heterotopic tracheal transplantation model was used. Protein concentrations of HMGB1, interferon-γ (IFN-γ), interleukin (IL)-10, and IL-17 were analyzed in the isografts, allografts, controls, and HMGB1-neutralizing antibody administered allografts (n = 6; Days 1, 3, 5, 7, 14, 21, and 28). The luminal fibrous occlusion was analyzed (n = 6; Days 7, 14, 21, and 28). Infiltrating CD8 and CD4 T lymphocytes around the allografts and serum levels of IFN-γ and IL-10 were evaluated (n = 6; Day 7). Results: The HMGB1 levels in the allografts were significantly increased compared with the isografts at Day 7. HMGB1 blockade did not change the IL-17 level, but decreased the IFN-γ/IL-10 ratio in the early phase (Days 5 and 7) and significantly improved the fibrous occlusion in the late phase (Days 14, 21, and 28). HMGB1 blockade significantly suppressed the CD8 T lymphocytes infiltration and decreased the serum IFN-γ/IL-10 ratio compared with the control at Day 7. Conclusions: HMGB1 may be a trigger of the BOS pathogenesis and candidate target for the treatment of the disease.

元の言語英語
ページ(範囲)13-20
ページ数8
ジャーナルTransplant Immunology
53
DOI
出版物ステータス出版済み - 4 2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Transplantation

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    Takamori, S., Shoji, F., Okamoto, T., Kozuma, Y., Matsubara, T., Haratake, N., Akamine, T., Katsura, M., Takada, K., Toyokawa, G., Tagawa, T., & Maehara, Y. (2019). HMGB1 blockade significantly improves luminal fibrous obliteration in a murine model of bronchiolitis obliterans syndrome. Transplant Immunology, 53, 13-20. https://doi.org/10.1016/j.trim.2018.11.007