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 journalArticlepeer-review

    35 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

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