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Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance.


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Authors

Abeler-Dörner, Lucie 
Chettle, James 
Mahlakõiv, Tanel 
Goubau, Delphine 

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.

Description

Keywords

Animals, Caliciviridae Infections, Cytokines, Epithelial Cells, Female, Gastroenteritis, Immunity, Innate, Interferon-alpha, Interferon-gamma, Interferons, Intestine, Small, Lymphocyte Activation, Lymphocytes, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Norovirus, T-Lymphocytes

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

6

Publisher

Springer Science and Business Media LLC
Sponsorship
Support was provided by the Wellcome Trust (A.C.H., J.L.H., G.R) and Cancer Research UK (A.C.H.), Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust (L.A.-D.; A.C.H.); Marie Curie and EMBO fellowships (M.S.).