title: Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance.
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.
authors.affiliation: Immunosurveillance lab, Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.|Peter Gorer Department of Immunobiology, King's College London, Borough Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.|Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Mahima
authors.identifier: 0000-0003-3977-3425
authors.initials: M
authors.lastname: Swamy
authors.affiliation: Immunosurveillance lab, Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.|Peter Gorer Department of Immunobiology, King's College London, Borough Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: Lucie
authors.initials: L
authors.lastname: Abeler-Dörner
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors.forename: James
authors.initials: J
authors.lastname: Chettle
authors.affiliation: Institute of Virology, University Medical Center, Freiburg D-79104, Germany.|Spemann Graduate School of Biology and Medicine, Albert Ludwigs University Freiburg, Freiburg, Germany.
authors.forename: Tanel
authors.initials: T
authors.lastname: Mahlakõiv
authors.affiliation: Immunosurveillance lab, Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.
authors.forename: Delphine
authors.initials: D
authors.lastname: Goubau
authors.affiliation: Immunosurveillance lab, Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.
authors.forename: Probir
authors.initials: P
authors.lastname: Chakravarty
authors.affiliation: Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: George
authors.initials: G
authors.lastname: Ramsay
authors.affiliation: Immunosurveillance lab, Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
authors.affiliation: Institute of Virology, University Medical Center, Freiburg D-79104, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Blacklaws
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
authors.affiliation: Immunosurveillance lab, Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.|Peter Gorer Department of Immunobiology, King's College London, Borough Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Hayday
mesh_terms: D000818:Animals; D017250:Caliciviridae Infections / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D005759:Gastroenteritis / Q000276:immunology* / Q000821:virology; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007372:Interferons / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D029322:Norovirus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D007371:Interferon-gamma; D007372:Interferons