Human but not mouse hepatocytes respond to interferon-lambda in vivo.

The type III interferon (IFN) receptor is preferentially expressed by epithelial cells. It is made of two subunits: IFNLR1, which is specific to IFN-lambda (IFN-λ) and IL10RB, which is shared by other cytokine receptors. Human hepatocytes express IFNLR1 and respond to IFN-λ. In contrast, the IFN-λ r...

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Main Authors: Pascale Hermant, Céline Demarez, Tanel Mahlakõiv, Peter Staeheli, Philip Meuleman, Thomas Michiels
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3909289?pdf=render
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author Pascale Hermant
Céline Demarez
Tanel Mahlakõiv
Peter Staeheli
Philip Meuleman
Thomas Michiels
author_facet Pascale Hermant
Céline Demarez
Tanel Mahlakõiv
Peter Staeheli
Philip Meuleman
Thomas Michiels
author_sort Pascale Hermant
collection DOAJ
description The type III interferon (IFN) receptor is preferentially expressed by epithelial cells. It is made of two subunits: IFNLR1, which is specific to IFN-lambda (IFN-λ) and IL10RB, which is shared by other cytokine receptors. Human hepatocytes express IFNLR1 and respond to IFN-λ. In contrast, the IFN-λ response of the mouse liver is very weak and IFNLR1 expression is hardly detectable in this organ. Here we investigated the IFN-λ response at the cellular level in the mouse liver and we tested whether human and mouse hepatocytes truly differ in responsiveness to IFN-λ. When monitoring expression of the IFN-responsive Mx genes by immunohistofluorescence, we observed that the IFN-λ response in mouse livers was restricted to cholangiocytes, which form the bile ducts, and that mouse hepatocytes were indeed not responsive to IFN-λ. The lack of mouse hepatocyte response to IFN-λ was observed in different experimental settings, including the infection with a hepatotropic strain of influenza A virus which triggered a strong local production of IFN-λ. With the help of chimeric mice containing transplanted human hepatocytes, we show that hepatocytes of human origin readily responded to IFN-λ in a murine environment. Thus, our data suggest that human but not mouse hepatocytes are responsive to IFN-λ in vivo. The non-responsiveness is an intrinsic property of mouse hepatocytes and is not due to the mouse liver micro-environment.
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spelling doaj.art-df4624e607d543ba8a605cb32f9f6d0c2022-12-21T19:38:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8790610.1371/journal.pone.0087906Human but not mouse hepatocytes respond to interferon-lambda in vivo.Pascale HermantCéline DemarezTanel MahlakõivPeter StaeheliPhilip MeulemanThomas MichielsThe type III interferon (IFN) receptor is preferentially expressed by epithelial cells. It is made of two subunits: IFNLR1, which is specific to IFN-lambda (IFN-λ) and IL10RB, which is shared by other cytokine receptors. Human hepatocytes express IFNLR1 and respond to IFN-λ. In contrast, the IFN-λ response of the mouse liver is very weak and IFNLR1 expression is hardly detectable in this organ. Here we investigated the IFN-λ response at the cellular level in the mouse liver and we tested whether human and mouse hepatocytes truly differ in responsiveness to IFN-λ. When monitoring expression of the IFN-responsive Mx genes by immunohistofluorescence, we observed that the IFN-λ response in mouse livers was restricted to cholangiocytes, which form the bile ducts, and that mouse hepatocytes were indeed not responsive to IFN-λ. The lack of mouse hepatocyte response to IFN-λ was observed in different experimental settings, including the infection with a hepatotropic strain of influenza A virus which triggered a strong local production of IFN-λ. With the help of chimeric mice containing transplanted human hepatocytes, we show that hepatocytes of human origin readily responded to IFN-λ in a murine environment. Thus, our data suggest that human but not mouse hepatocytes are responsive to IFN-λ in vivo. The non-responsiveness is an intrinsic property of mouse hepatocytes and is not due to the mouse liver micro-environment.http://europepmc.org/articles/PMC3909289?pdf=render
spellingShingle Pascale Hermant
Céline Demarez
Tanel Mahlakõiv
Peter Staeheli
Philip Meuleman
Thomas Michiels
Human but not mouse hepatocytes respond to interferon-lambda in vivo.
PLoS ONE
title Human but not mouse hepatocytes respond to interferon-lambda in vivo.
title_full Human but not mouse hepatocytes respond to interferon-lambda in vivo.
title_fullStr Human but not mouse hepatocytes respond to interferon-lambda in vivo.
title_full_unstemmed Human but not mouse hepatocytes respond to interferon-lambda in vivo.
title_short Human but not mouse hepatocytes respond to interferon-lambda in vivo.
title_sort human but not mouse hepatocytes respond to interferon lambda in vivo
url http://europepmc.org/articles/PMC3909289?pdf=render
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AT peterstaeheli humanbutnotmousehepatocytesrespondtointerferonlambdainvivo
AT philipmeuleman humanbutnotmousehepatocytesrespondtointerferonlambdainvivo
AT thomasmichiels humanbutnotmousehepatocytesrespondtointerferonlambdainvivo