Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance

Mahima Swamy (Lead / Corresponding author), 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, Adrian C. Hayday (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    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.

    Original languageEnglish
    Article number7090
    Number of pages12
    JournalNature Communications
    Volume6
    DOIs
    Publication statusPublished - 19 May 2015

    Fingerprint

    Lymphocytes
    lymphocytes
    Lymphocyte Activation
    Antiviral Agents
    interferon
    Epithelial Cells
    Chemical activation
    activation
    epithelium
    Interferons
    T-cells
    Up-Regulation
    Epithelium
    Interferon alpha-beta Receptor
    Cytokines
    T-Lymphocytes
    Norovirus
    infectious diseases
    Lymphokines
    Genes

    Cite this

    Swamy, M., Abeler-Dörner, L., Chettle, J., Mahlakõiv, T., Goubau, D., Chakravarty, P., ... Hayday, A. C. (2015). Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance. Nature Communications, 6, [7090]. https://doi.org/10.1038/ncomms8090
    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. / Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance. In: Nature Communications. 2015 ; Vol. 6.
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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.",
    author = "Mahima Swamy and Lucie Abeler-D{\"o}rner and James Chettle and Tanel Mahlak{\~o}iv and Delphine Goubau and Probir Chakravarty and George Ramsay and {Reis e Sousa}, Caetano and Peter Staeheli and Blacklaws, {Barbara A.} and Heeney, {Jonathan L.} and Hayday, {Adrian C.}",
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    Swamy, M, Abeler-Dörner, L, Chettle, J, Mahlakõiv, T, Goubau, D, Chakravarty, P, Ramsay, G, Reis e Sousa, C, Staeheli, P, Blacklaws, BA, Heeney, JL & Hayday, AC 2015, 'Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance', Nature Communications, vol. 6, 7090. https://doi.org/10.1038/ncomms8090

    Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance. / Swamy, Mahima (Lead / Corresponding author); 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. (Lead / Corresponding author).

    In: Nature Communications, Vol. 6, 7090, 19.05.2015.

    Research output: Contribution to journalArticle

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    AU - Staeheli, Peter

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    AU - Hayday, Adrian C.

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    Swamy M, Abeler-Dörner L, Chettle J, Mahlakõiv T, Goubau D, Chakravarty P et al. Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance. Nature Communications. 2015 May 19;6. 7090. https://doi.org/10.1038/ncomms8090