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Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function

Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Us...

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Autores principales: Sander, Leif E., Sackett, Sara Dutton, Dierssen, Uta, Beraza, Naiara, Linke, Reinhold P., Müller, Michael, Blander, J. Magarian, Tacke, Frank, Trautwein, Christian
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901069/
https://www.ncbi.nlm.nih.gov/pubmed/20530204
http://dx.doi.org/10.1084/jem.20091474
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author Sander, Leif E.
Sackett, Sara Dutton
Dierssen, Uta
Beraza, Naiara
Linke, Reinhold P.
Müller, Michael
Blander, J. Magarian
Tacke, Frank
Trautwein, Christian
author_facet Sander, Leif E.
Sackett, Sara Dutton
Dierssen, Uta
Beraza, Naiara
Linke, Reinhold P.
Müller, Michael
Blander, J. Magarian
Tacke, Frank
Trautwein, Christian
author_sort Sander, Leif E.
collection PubMed
description Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a mouse model of polymicrobial sepsis, we show that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6 family cytokines, strongly increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through STAT3 was required to control systemic inflammation. Notably, hepatic gp130–STAT3 activation was also essential for mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for antiinflammatory properties in cancer. MDSCs were critical to regulate innate inflammation, and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. The hepatic APPs serum amyloid A and Cxcl1/KC cooperatively promoted MDSC mobilization, accumulation, and survival, and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through APPs controls inflammatory responses during infection.
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spelling pubmed-29010692011-01-05 Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function Sander, Leif E. Sackett, Sara Dutton Dierssen, Uta Beraza, Naiara Linke, Reinhold P. Müller, Michael Blander, J. Magarian Tacke, Frank Trautwein, Christian J Exp Med Article Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a mouse model of polymicrobial sepsis, we show that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6 family cytokines, strongly increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through STAT3 was required to control systemic inflammation. Notably, hepatic gp130–STAT3 activation was also essential for mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for antiinflammatory properties in cancer. MDSCs were critical to regulate innate inflammation, and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. The hepatic APPs serum amyloid A and Cxcl1/KC cooperatively promoted MDSC mobilization, accumulation, and survival, and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through APPs controls inflammatory responses during infection. The Rockefeller University Press 2010-07-05 /pmc/articles/PMC2901069/ /pubmed/20530204 http://dx.doi.org/10.1084/jem.20091474 Text en © 2010 Sander et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Sander, Leif E.
Sackett, Sara Dutton
Dierssen, Uta
Beraza, Naiara
Linke, Reinhold P.
Müller, Michael
Blander, J. Magarian
Tacke, Frank
Trautwein, Christian
Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
title Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
title_full Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
title_fullStr Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
title_full_unstemmed Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
title_short Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
title_sort hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901069/
https://www.ncbi.nlm.nih.gov/pubmed/20530204
http://dx.doi.org/10.1084/jem.20091474
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