Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistanceMore about Open Access at the Crick
Authors listMahima 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 Adrian Hayday
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.
Journal Nature Communications