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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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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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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issn | 1932-6203 |
language | English |
last_indexed | 2024-12-20T14:16:55Z |
publishDate | 2014-01-01 |
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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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