Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance

Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregu...

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Published inNature communications Vol. 6; no. 1; p. 7090
Main Authors Swamy, Mahima, Abeler-Dörner, Lucie, Chettle, James, Mahlakõiv, Tanel, Goubau, Delphine, Chakravarty, Probir, Ramsay, George, Reis e Sousa, Caetano, Staeheli, Peter, Blacklaws, Barbara A., Heeney, Jonathan L., Hayday, Adrian C.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 19.05.2015
Nature Publishing Group
Nature Pub. Group
Subjects
13/106
13/21
13/51
14/19
38/61
38/77
631/250/127/1212
631/250/1619/554
631/250/347
631/326/22/1434
64/110
64/60
82/29
96/1
96/31
Animals
Antiviral drugs
Biology
Caliciviridae Infections - immunology
Cell activation
Cytokines
Cytokines - metabolism
Cytolysis
Cytotoxicity
Epithelial cells
Epithelial Cells - immunology
Epithelium
Female
Gastroenteritis - immunology
Gastroenteritis - virology
Gene expression
Genes
Humanities and Social Sciences
Immune system
Immunity, Innate
Infections
Interferon
Interferon-alpha - metabolism
Interferon-gamma - metabolism
Interferons - metabolism
Intestine
Intestine, Small - metabolism
Lymphocyte Activation
Lymphocytes
Lymphocytes - immunology
Lymphocytes T
Macrophages - cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
multidisciplinary
Norovirus - immunology
Science
Science (multidisciplinary)
T-Lymphocytes - immunology
Villus
Viruses
Online AccessGet full text

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Abstract Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro , and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium. Intraepithelial lymphocytes in the gut eliminate dysfunctional epithelial cells and promote regrowth of healthy cells. Here the authors show that, in addition, these lymphocytes protect cells against viral infections by rapidly activating interferon-dependent pathways in intestinal epithelial cells.
AbstractList Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium.
Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro , and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium.
Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro , and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium. Intraepithelial lymphocytes in the gut eliminate dysfunctional epithelial cells and promote regrowth of healthy cells. Here the authors show that, in addition, these lymphocytes protect cells against viral infections by rapidly activating interferon-dependent pathways in intestinal epithelial cells.
Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium.Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium.
ArticleNumber 7090
Author Goubau, Delphine
Ramsay, George
Chakravarty, Probir
Staeheli, Peter
Abeler-Dörner, Lucie
Heeney, Jonathan L.
Swamy, Mahima
Hayday, Adrian C.
Mahlakõiv, Tanel
Blacklaws, Barbara A.
Chettle, James
Reis e Sousa, Caetano
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  organization: Immunosurveillance lab, Francis Crick Institute, Peter Gorer Department of Immunobiology, King’s College London, Borough Wing, Guy’s Hospital, Great Maze Pond, Cell Signalling and Immunology, College of Life Sciences, University of Dundee
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  fullname: Chakravarty, Probir
  organization: Immunosurveillance lab, Francis Crick Institute
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  organization: Cell Signalling and Immunology, College of Life Sciences, University of Dundee
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  email: adrian.hayday@kcl.ac.uk
  organization: Immunosurveillance lab, Francis Crick Institute, Peter Gorer Department of Immunobiology, King’s College London, Borough Wing, Guy’s Hospital, Great Maze Pond
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25987506$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright The Author(s) 2015
Copyright Nature Publishing Group May 2015
Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
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Snippet Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial...
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SubjectTerms 13/106
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Animals
Antiviral drugs
Biology
Caliciviridae Infections - immunology
Cell activation
Cytokines
Cytokines - metabolism
Cytolysis
Cytotoxicity
Epithelial cells
Epithelial Cells - immunology
Epithelium
Female
Gastroenteritis - immunology
Gastroenteritis - virology
Gene expression
Genes
Humanities and Social Sciences
Immune system
Immunity, Innate
Infections
Interferon
Interferon-alpha - metabolism
Interferon-gamma - metabolism
Interferons - metabolism
Intestine
Intestine, Small - metabolism
Lymphocyte Activation
Lymphocytes
Lymphocytes - immunology
Lymphocytes T
Macrophages - cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
multidisciplinary
Norovirus - immunology
Science
Science (multidisciplinary)
T-Lymphocytes - immunology
Villus
Viruses
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Title Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance
URI https://link.springer.com/article/10.1038/ncomms8090
https://www.ncbi.nlm.nih.gov/pubmed/25987506
https://www.proquest.com/docview/1681488686
https://www.proquest.com/docview/1682204467
https://pubmed.ncbi.nlm.nih.gov/PMC4479038
Volume 6
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