Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance

Mahima Swamy (), Lucie Abeler-Dörner, James Chettle, Tanel Mahlakõiv, Delphine Goubau, Probir Chakravarty, George Ramsay, Caetano Reis e Sousa, Peter Staeheli, Barbara A. Blacklaws, Jonathan L. Heeney and Adrian C. Hayday ()
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Mahima Swamy: Immunosurveillance lab, Francis Crick Institute
Lucie Abeler-Dörner: Immunosurveillance lab, Francis Crick Institute
James Chettle: University of Cambridge
Tanel Mahlakõiv: Institute of Virology, University Medical Center
Delphine Goubau: Immunosurveillance lab, Francis Crick Institute
Probir Chakravarty: Immunosurveillance lab, Francis Crick Institute
George Ramsay: Cell Signalling and Immunology, College of Life Sciences, University of Dundee
Caetano Reis e Sousa: Immunosurveillance lab, Francis Crick Institute
Peter Staeheli: Institute of Virology, University Medical Center
Barbara A. Blacklaws: University of Cambridge
Jonathan L. Heeney: University of Cambridge
Adrian C. Hayday: Immunosurveillance lab, Francis Crick Institute

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8090

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