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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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Autores principales: Hermant, Pascale, Demarez, Céline, Mahlakõiv, Tanel, Staeheli, Peter, Meuleman, Philip, Michiels, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909289/
https://www.ncbi.nlm.nih.gov/pubmed/24498220
http://dx.doi.org/10.1371/journal.pone.0087906
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author Hermant, Pascale
Demarez, Céline
Mahlakõiv, Tanel
Staeheli, Peter
Meuleman, Philip
Michiels, Thomas
author_facet Hermant, Pascale
Demarez, Céline
Mahlakõiv, Tanel
Staeheli, Peter
Meuleman, Philip
Michiels, Thomas
author_sort Hermant, Pascale
collection PubMed
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 pubmed-39092892014-02-04 Human but Not Mouse Hepatocytes Respond to Interferon-Lambda In Vivo Hermant, Pascale Demarez, Céline Mahlakõiv, Tanel Staeheli, Peter Meuleman, Philip Michiels, Thomas PLoS One Research Article 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. Public Library of Science 2014-01-31 /pmc/articles/PMC3909289/ /pubmed/24498220 http://dx.doi.org/10.1371/journal.pone.0087906 Text en © 2014 Hermant et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hermant, Pascale
Demarez, Céline
Mahlakõiv, Tanel
Staeheli, Peter
Meuleman, Philip
Michiels, Thomas
Human but Not Mouse Hepatocytes Respond to Interferon-Lambda In Vivo
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909289/
https://www.ncbi.nlm.nih.gov/pubmed/24498220
http://dx.doi.org/10.1371/journal.pone.0087906
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