These authors contributed equally to this work.
1527-3350/asset/olbannerleft.gif?v=1&s=4b2409f9534ed500d3c8da1940a23842e2b9932d)
1527-3350/asset/olbannerright.gif?v=1&s=141b9a8485298533c3e2016e937b0404f7d933e1)
Liver Injury/Regeneration
You have full text access to this OnlineOpen article
Hepatic B7 homolog 1 expression is essential for controlling cold ischemia/reperfusion injury after mouse liver transplantation†‡
Article first published online: 24 JUN 2011
DOI: 10.1002/hep.24360
Copyright © 2011 American Association for the Study of Liver Diseases
Additional Information
How to Cite
Ueki, S., Castellaneta, A., Yoshida, O., Ozaki, K., Zhang, M., Kimura, S., Isse, K., Ross, M., Shao, L., Stolz, D. B., Thomson, A. W., Demetris, A. J., Geller, D. A. and Murase, N. (2011), Hepatic B7 homolog 1 expression is essential for controlling cold ischemia/reperfusion injury after mouse liver transplantation. Hepatology, 54: 216–228. doi: 10.1002/hep.24360
- †
Potential conflict of interest: Nothing to report.
- ‡
This work was supported by the National Institutes of Health (through grant P01AI081678-02 to Angus W. Thomson and through grant DK071753 to Noriko Murase). Shinya Ueki was supported by a postdoctoral fellowship from the Thomas E. Starzl Transplantation Institute. Antonino Castellaneta was supported by a Basic Science Fellowship from the American Society of Transplantation, by a Sunflowers for Holli Fellowship from the American Liver Foundation, and by a Young Investigator Grant from the Thomas E. Starzl Transplantation Institute.
- §
These authors contributed equally to this work.
- ¶
fax: 412-624-6666
Publication History
- Issue published online: 24 JUN 2011
- Article first published online: 24 JUN 2011
- Accepted manuscript online: 18 APR 2011 08:32AM EST
- Manuscript Accepted: 2 APR 2011
- Manuscript Received: 19 NOV 2010
- Abstract
- Article
- References
- Cited By
Abstract
Ischemia/reperfusion (I/R) injury remains a key risk factor significantly affecting morbidity and mortality after liver transplantation (LT). B7 homolog 1 (B7-H1), a recently identified member of the B7 family, is known to play important roles in regulating local immune responses. We hypothesized that B7-H1 plays crucial roles during innate immune responses induced by hepatic I/R injury, and using B7-H1 knockout (KO) liver grafts, we tested this hypothesis in the mouse LT model with 24 hours of cold storage. Cold I/R injury in wild type (WT)-to-WT LT enhanced constitutive B7-H1 expression on dendritic cells and sinusoidal endothelial cells and promptly induced B7-H1 on hepatocytes. When B7-H1 KO liver grafts were transplanted into WT recipients, serum alanine aminotransferase (ALT) and graft necrosis levels were significantly higher than those after WT-to-WT LT. Augmented tissue injury in B7-H1 KO grafts was associated with increased frequencies and absolute numbers of graft CD3+ T cells (particularly CD8+ T cells). B7-H1 KO grafts had significantly fewer annexin V+ CD8+ T cells, and this indicated a failure to delete infiltrating CD8+ T cells. To evaluate the relative contributions of parenchymal cell and bone marrow–derived cell (BMDC) B7-H1 expression, we generated and transplanted into WT recipients chimeric liver grafts lacking B7-H1 on parenchymal cells or BMDCs. A selective B7-H1 deficiency on parenchymal cells or BMDCs resulted in similar levels of ALT and liver injury, and this suggested that parenchymal cell and BMDC B7-H1 expression was involved in liver damage control. Human livers up-regulated B7-H1 expression after LT. Conclusion: The study demonstrates that graft tissue expression of B7-H1 plays a critical role in regulating inflammatory responses during LT-induced hepatic I/R injury, and negative coregulatory signals may have an important function in hepatic innate immune responses. (HEPATOLOGY 2011;)