dc.contributor.author |
Welz, M |
|
dc.contributor.author |
Eickhoff, S |
|
dc.contributor.author |
Abdullah, Z |
|
dc.contributor.author |
Trebicka, J |
|
dc.contributor.author |
Gartlan, KH |
|
dc.contributor.author |
Spicer, JA |
|
dc.contributor.author |
Demetris, AJ |
|
dc.contributor.author |
Akhlaghi, H |
|
dc.contributor.author |
Anton, M |
|
dc.contributor.author |
Manske, K |
|
dc.contributor.author |
Zehn, D |
|
dc.contributor.author |
Nieswandt, B |
|
dc.contributor.author |
Kurts, C |
|
dc.contributor.author |
Trapani, JA |
|
dc.contributor.author |
Knolle, P |
|
dc.contributor.author |
Wohlleber, D |
|
dc.contributor.author |
Kastenmüller, W |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2020-12-08T02:08:11Z |
|
dc.date.available |
2020-12-08T02:08:11Z |
|
dc.date.issued |
2018-11-15 |
|
dc.identifier.citation |
Nature communications 9(1):4805 15 Nov 2018 |
|
dc.identifier.issn |
2041-1723 |
|
dc.identifier.uri |
http://hdl.handle.net/2292/53807 |
|
dc.description.abstract |
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. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
Springer Science and Business Media LLC |
|
dc.relation.ispartofseries |
Nature communications |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Liver |
|
dc.subject |
Capillaries |
|
dc.subject |
CD8-Positive T-Lymphocytes |
|
dc.subject |
Endothelial Cells |
|
dc.subject |
Hepatocytes |
|
dc.subject |
Animals |
|
dc.subject |
Mice, Inbred C57BL |
|
dc.subject |
Mice, Knockout |
|
dc.subject |
Humans |
|
dc.subject |
Mice |
|
dc.subject |
Adenoviridae |
|
dc.subject |
Hepatitis, Viral, Animal |
|
dc.subject |
Disease Models, Animal |
|
dc.subject |
Sulfonamides |
|
dc.subject |
Luciferases |
|
dc.subject |
Ovalbumin |
|
dc.subject |
Green Fluorescent Proteins |
|
dc.subject |
Poly I-C |
|
dc.subject |
Antibodies |
|
dc.subject |
Protective Agents |
|
dc.subject |
Gene Expression |
|
dc.subject |
Genes, Reporter |
|
dc.subject |
Pore Forming Cytotoxic Proteins |
|
dc.subject |
CD40 Antigens |
|
dc.subject |
Adenoviridae |
|
dc.subject |
Animals |
|
dc.subject |
Antibodies |
|
dc.subject |
CD40 Antigens |
|
dc.subject |
CD8-Positive T-Lymphocytes |
|
dc.subject |
Capillaries |
|
dc.subject |
Disease Models, Animal |
|
dc.subject |
Endothelial Cells |
|
dc.subject |
Gene Expression |
|
dc.subject |
Genes, Reporter |
|
dc.subject |
Green Fluorescent Proteins |
|
dc.subject |
Hepatitis, Viral, Animal |
|
dc.subject |
Hepatocytes |
|
dc.subject |
Humans |
|
dc.subject |
Liver |
|
dc.subject |
Luciferases |
|
dc.subject |
Mice |
|
dc.subject |
Mice, Inbred C57BL |
|
dc.subject |
Mice, Knockout |
|
dc.subject |
Ovalbumin |
|
dc.subject |
Poly I-C |
|
dc.subject |
Pore Forming Cytotoxic Proteins |
|
dc.subject |
Protective Agents |
|
dc.subject |
Sulfonamides |
|
dc.subject |
Science & Technology |
|
dc.subject |
Multidisciplinary Sciences |
|
dc.subject |
Science & Technology - Other Topics |
|
dc.subject |
CYTOTOXIC T-LYMPHOCYTES |
|
dc.subject |
CROSS-PRESENTATION |
|
dc.subject |
VIRUS-INFECTION |
|
dc.subject |
LIVER-DAMAGE |
|
dc.subject |
KILLER-CELL |
|
dc.subject |
B-VIRUS |
|
dc.subject |
LIGAND |
|
dc.subject |
MICE |
|
dc.subject |
FAS |
|
dc.subject |
INVOLVEMENT |
|
dc.subject |
1107 Immunology |
|
dc.subject |
1103 Clinical Sciences |
|
dc.subject |
Biomedical |
|
dc.subject |
Basic Science |
|
dc.subject |
Infectious Diseases |
|
dc.subject |
Chronic Liver Disease and Cirrhosis |
|
dc.subject |
Hepatitis |
|
dc.subject |
Liver Disease |
|
dc.subject |
Digestive Diseases |
|
dc.subject |
Infection |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.title |
Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1038/s41467-018-07213-x |
|
pubs.issue |
1 |
|
pubs.begin-page |
4805 |
|
pubs.volume |
9 |
|
dc.date.updated |
2020-11-26T17:48:59Z |
|
dc.rights.holder |
Copyright: The author |
en |
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/30442932 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
|
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
757216 |
|
dc.identifier.eissn |
2041-1723 |
|
dc.identifier.pii |
10.1038/s41467-018-07213-x |
|
pubs.number |
4805 |
|
pubs.online-publication-date |
2018-11-15 |
|