論文

査読有り
2014年9月

Programmed Death-1 Pathway in Host Tissues Ameliorates Th17/Th1-Mediated Experimental Chronic Graft-versus-Host Disease

JOURNAL OF IMMUNOLOGY
  • Hideaki Fujiwara
  • ,
  • Yoshinobu Maeda
  • ,
  • Koichiro Kobayashi
  • ,
  • Hisakazu Nishimori
  • ,
  • Ken-ichi Matsuoka
  • ,
  • Nobuharu Fujii
  • ,
  • Eisei Kondo
  • ,
  • Takehiro Tanaka
  • ,
  • Lieping Chen
  • ,
  • Miyuki Azuma
  • ,
  • Hideo Yagita
  • ,
  • Mitsune Tanimoto

193
5
開始ページ
2565
終了ページ
2573
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.4049/jimmunol.1400954
出版者・発行元
AMER ASSOC IMMUNOLOGISTS

Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the role of the programmed death-1 (PD-1) pathway in chronic GVHD using a well-defined mouse model of B10.D2 (H-2(d)) donor to BALB/c (H-2(d)) recipients. PD-1 expression on allogeneic donor T cells was upregulated continuously in chronic GVHD development, whereas PD-L1 expression in host tissues was transiently upregulated and declined to basal levels in the late posttransplant period. Blockade of the PD-1 pathway by anti-PD-1, anti-PD-L1, or anti-PD-L2 mAbs exacerbated clinical and pathologic chronic GVHD. Chimeric mice revealed that PD-L1 expression in host tissues suppressed expansion of IL-17(+)IFN-gamma(+) T cells, and that PD-L1 expression on hematopoietic cells plays a role in the development of regulatory T cells only during the early transplantation period but does not affect the severity of chronic GVHD. Administration of the synthetic retinoid Am80 overcame the IL-17(+)IFN-gamma(+) T cell expansion caused by PD-L1 deficiency, resulting in reduced chronic GVHD damage in PD-L1(-/-) recipients. Stimulation of the PD-1 pathway also alleviated chronic GVHD. These results suggest that the PD-1 pathway contributes to the suppression of Th17/Th1-mediated chronic GVHD and may represent a new target for the prevention or treatment of chronic GVHD.

Web of Science ® 被引用回数 : 38

リンク情報
DOI
https://doi.org/10.4049/jimmunol.1400954
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000341140600057&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-84907021169&partnerID=MN8TOARS
URL
http://orcid.org/0000-0003-0995-9405

エクスポート
BibTeX RIS