Hepatic B7 homolog 1 expression is essential for controlling cold ischemia/reperfusion injury after mouse liver transplantation.
Hepatic B7 homolog 1 expression is essential for controlling cold ischemia/reperfusion injury after mouse liver transplantation.
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DOI：
10.1002/hep.24360
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发表时间：
2011-07
期刊：
影响因子：
13.5
通讯作者：
Murase, Noriko
中科院分区：
文献类型：
--
作者：
Ueki, Shinya;Castellaneta, Antonino;Yoshida, Osamu;Ozaki, Kikumi;Zhang, Matthew;Kimura, Shoko;Isse, Kumiko;Ross, Mark;Shao, Lifang;Stolz, Donna B.;Thomson, Angus W.;Demetris, Anthony J.;Geller, David A.;Murase, Noriko
缺血/再灌注(I/R)损伤仍然是影响肝移植(LTX)术后发病率和死亡率的重要危险因素。B7-H1是新近发现的B7家族成员，在调节局部免疫反应中发挥重要作用。我们假设B7-H1在肝脏I/R损伤诱导的先天免疫反应中发挥关键作用，并在使用B7-H1 KO肝移植24小时冷藏的小鼠LTX模型中验证了这一假设。WT至WT LTX冷I/R损伤后，树突状细胞和肝窦内皮细胞B7-H1的表达增加，肝细胞上B7-H1的表达也迅速增加。B7-H1 KO肝移植到WT受体后，血清ALT水平和移植物坏死率均显著高于WT-LTX组。B7-H1KO移植物的组织损伤增加与移植物CD3+T细胞，尤其是CD8+T细胞的频率和绝对数增加有关。B7-H1KO移植物Annexin V+CD8+T细胞比例明显降低，提示未能清除浸润性CD8+T细胞。为了评估实质细胞和骨髓来源细胞(BMDC)B7-H1表达的相对贡献，在实质细胞或BMDC上构建了缺失B7-H1的嵌合肝移植，并将其移植到WT受者体内。实质细胞或BMDC的选择性B7-H1缺失可导致相似水平的ALT和肝损伤，提示实质细胞和BMDC B7-H1的表达均参与了肝损伤的控制。人肝移植后B7-H1表达上调。结论：移植肝组织中B7-H1的表达在LTX诱导的肝脏I/R损伤的炎症反应中起着重要的调节作用，提示负调控信号在肝脏固有免疫反应中可能具有重要作用。
Ischemia/reperfusion (I/R) injury remains a key risk factor significantly affecting morbidity and mortality after liver transplantation (LTx). B7-H1, 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 tested this hypothesis in the mouse LTx model using B7-H1 KO liver grafts with 24 hr cold storage. Cold I/R injury in WT to WT LTx 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 ALT levels and graft necrosis were significantly higher than WT to WT LTx. Augmented tissue injury in B7-H1 KO grafts was associated with increased frequencies and absolute numbers of graft CD3+ T cells, in particular CD8+ T cells. B7-H1 KO grafts had significantly lower incidences of Annexin V+ CD8+ T cells, indicating the failure to delete infiltrating CD8+ T cells. To evaluate the relative contribution of parenchymal and bone marrow-derived cell (BMDC) B7-H1 expression, chimeric liver grafts lacking B7-H1 on parenchymal cells or BMDC were generated and transplanted into WT recipients. Selective B7-H1 deficiency on parenchymal cells or BMDC resulted in similar levels of ALT and liver injury, suggesting that both parenchymal and BMDC B7-H1expression is involved in the control of liver damage. Human livers upregulated B7-H1 expression after LTx. Conclusion: The study demonstrates that graft tissue expression of B7-H1 plays critical roles in regulating inflammatory responses during LTx-induced hepatic I/R injury, and suggests that negative coregulatory signals may have an important function in hepatic innate immune responses.
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影响因子：
32.4
作者：
Dong, HD;Zhu, GF;Chen, LP
通讯作者：
Chen, LP
DOI：
10.1111/j.1600-6143.2009.02859.x
发表时间：
2010-01
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Morita M;Fujino M;Jiang G;Kitazawa Y;Xie L;Azuma M;Yagita H;Nagao S;Sugioka A;Kurosawa Y;Takahara S;Fung J;Qian S;Lu L;Li XK
通讯作者：
Li XK
影响因子：
3.5
作者：
Lee, SJ;Jang, BC;Choi, IH
通讯作者：
Choi, IH
DOI：
10.4049/jimmunol.0900582
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castellaneta A;Sumpter TL;Chen L;Tokita D;Thomson AW
通讯作者：
Thomson AW
影响因子：
13.5
作者：
Shen, XD;Ke, BB;Kupiec-Weglinski, JW
通讯作者：
Kupiec-Weglinski, JW