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Nat Commun. 2015 May 19;6:7090. doi: 10.1038/ncomms8090.

Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance.

Author information

1
1] Immunosurveillance lab, Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK [2] Peter Gorer Department of Immunobiology, King's College London, Borough Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK [3] Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
2
1] Immunosurveillance lab, Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK [2] Peter Gorer Department of Immunobiology, King's College London, Borough Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
3
Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
4
1] Institute of Virology, University Medical Center, Freiburg D-79104, Germany [2] Spemann Graduate School of Biology and Medicine, Albert Ludwigs University Freiburg, Freiburg, Germany.
5
Immunosurveillance lab, Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.
6
Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
7
Institute of Virology, University Medical Center, Freiburg D-79104, Germany.

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.

PMID:
25987506
PMCID:
PMC4479038
DOI:
10.1038/ncomms8090
[Indexed for MEDLINE]
Free PMC Article

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