TY - JOUR
T1 - Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance
AU - Swamy, Mahima
AU - Abeler-Dörner, Lucie
AU - Chettle, James
AU - Mahlakõiv, Tanel
AU - Goubau, Delphine
AU - Chakravarty, Probir
AU - Ramsay, George
AU - Reis e Sousa, Caetano
AU - Staeheli, Peter
AU - Blacklaws, Barbara A.
AU - Heeney, Jonathan L.
AU - Hayday, Adrian C.
PY - 2015/5/19
Y1 - 2015/5/19
N2 - 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.
AB - 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.
U2 - 10.1038/ncomms8090
DO - 10.1038/ncomms8090
M3 - Article
C2 - 25987506
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 7090
ER -
