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DOI | 10.1038/s41467-018-06120-5 |
Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis | |
Welz, M.1; Eickhoff, S.1; Abdullah, Z.1; Trebicka, J.2,3; Gartlan, K. H.4; Spicer, J. A.5,6; Demetris, A. J.; Akhlaghi, H.7; Anton, M.8; Manske, K.8; Zehn, D.9; Nieswandt, B.10; Kurts, C.1; Trapani, J. A.7; Knolle, P.8; Wohlleber, D.; Kastenmueller, W.1,11 | |
2018-11-15 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Germany; Spain; Australia; New Zealand; USA |
英文摘要 | CD8 T cells protect the liver against viral infection, but can also cause severe liver damage that may even lead to organ failure. Given the lack of mechanistic insights and specific treatment options in patients with acute fulminant hepatitis, we develop a mouse model reflecting a severe acute virus-induced CD8 T cell-mediated hepatitis. Here we show that antigen-specific CD8 T cells induce liver damage in a perforin-dependent manner, yet liver failure is not caused by effector responses targeting virus-infected hepatocytes alone. Additionally, CD8 T cell mediated elimination of cross-presenting liver sinusoidal endothelial cells causes endothelial damage that leads to a dramatically impaired sinusoidal perfusion and indirectly to hepatocyte death. With the identification of perforin-mediated killing as a critical pathophysiologic mechanism of liver failure and the protective function of a new class of perforin inhibitor, our study opens new potential therapeutic angles for fulminant viral hepatitis. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000450161100005 |
WOS关键词 | CYTOTOXIC T-LYMPHOCYTES ; CROSS-PRESENTATION ; VIRUS-INFECTION ; LIVER-DAMAGE ; KILLER-CELL ; B-VIRUS ; LIGAND ; MICE ; FAS ; INVOLVEMENT |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203999 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Bonn, Inst Expt Immunol, Univ Hosp, D-53127 Bonn, Germany; 2.Univ Bonn, Dept Internal Med 1, D-53127 Bonn, Germany; 3.European Fdn Study Chron Liver Failure, Barcelona 08021, Spain; 4.QIMR Berghofer Med Res Inst, 300 Herston Rd QLD, Herston, Qld 4006, Australia; 5.Univ Auckland, Auckland Canc Soc, Res Ctr, Auckland 92019, New Zealand; 6.Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA; 7.Peter MacCallum Canc Ctr, Melbourne, Vic 3000, Australia; 8.Tech Univ Munich, Inst Mol Immunol & Expt Oncol, Klinikum Rechts Isar, D-81675 Munich, Germany; 9.Tech Univ Munich, Div Anim Physiol & Immunol, Sch Life Sci Weihenstephan, Weihenstephaner Berg 3, D-85354 Freising Weihenstephan, Germany; 10.Univ Wurzburg, Inst Expt Biomed 1, D-97078 Wurzburg, Germany; 11.Univ Wurzburg, Inst Syst Immunol, D-97078 Wurzburg, Germany |
推荐引用方式 GB/T 7714 | Welz, M.,Eickhoff, S.,Abdullah, Z.,et al. Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Welz, M..,Eickhoff, S..,Abdullah, Z..,Trebicka, J..,Gartlan, K. H..,...&Kastenmueller, W..(2018).Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis.NATURE COMMUNICATIONS,9. |
MLA | Welz, M.,et al."Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis".NATURE COMMUNICATIONS 9(2018). |
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