{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:43:12Z","timestamp":1790253792396,"version":"4.1.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T00:00:00Z","timestamp":1431993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T00:00:00Z","timestamp":1431993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 <jats:italic>in vivo<\/jats:italic> 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 <jats:italic>in vitro<\/jats:italic>, and pre-activation of IEL <jats:italic>in vivo<\/jats:italic> profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium.<\/jats:p>","DOI":"10.1038\/ncomms8090","type":"journal-article","created":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T10:19:51Z","timestamp":1432030791000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3977-3425","authenticated-orcid":false,"given":"Mahima","family":"Swamy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Abeler-D\u00f6rner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Chettle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanel","family":"Mahlak\u00f5iv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Goubau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Probir","family":"Chakravarty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Ramsay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caetano","family":"Reis e Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Staeheli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Blacklaws","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Heeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian C.","family":"Hayday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,5,19]]},"reference":[{"key":"BFncomms8090_CR1","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/ni1101-997","volume":"2","author":"A Hayday","year":"2001","unstructured":"Hayday, A., Theodoridis, E., Ramsburg, E. & Shires, J. Intraepithelial lymphocytes: exploring the Third Way in immunology. Nat. Immunol. 2, 997\u20131003 (2001).","journal-title":"Nat. Immunol."},{"key":"BFncomms8090_CR2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.it.2012.08.008","volume":"34","author":"T Gebhardt","year":"2013","unstructured":"Gebhardt, T., Mueller, S. N., Heath, W. R. & Carbone, F. R. Peripheral tissue surveillance and residency by memory T cells. Trends Immunol. 34, 27\u201332 (2013).","journal-title":"Trends Immunol."},{"key":"BFncomms8090_CR3","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/mi.2008.8","volume":"1","author":"A Hayday","year":"2008","unstructured":"Hayday, A. & Gibbons, D. Brokering the peace: the origin of intestinal T cells. Mucosal Immunol. 1, 172\u2013174 (2008).","journal-title":"Mucosal Immunol."},{"key":"BFncomms8090_CR4","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nri3007","volume":"11","author":"H Cheroutre","year":"2011","unstructured":"Cheroutre, H., Lambolez, F. & Mucida, D. The light and dark sides of intestinal intraepithelial lymphocytes. Nat. Rev. Immunol. 11, 445\u2013456 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8090_CR5","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.immuni.2009.08.006","volume":"31","author":"AC Hayday","year":"2009","unstructured":"Hayday, A. C. \u03b3\u03b4 T cells and the lymphoid stress-surveillance response. Immunity 31, 184\u2013196 (2009).","journal-title":"Immunity"},{"key":"BFncomms8090_CR6","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/S1074-7613(01)00192-3","volume":"15","author":"J Shires","year":"2001","unstructured":"Shires, J., Theodoridis, E. & Hayday, A. C. Biological insights into TCR\u03b3\u03b4+ and TCR\u03b1\u03b2+ intraepithelial lymphocytes provided by serial analysis of gene expression (SAGE). Immunity 15, 419\u2013434 (2001).","journal-title":"Immunity"},{"key":"BFncomms8090_CR7","doi-asserted-by":"publisher","first-page":"14338","DOI":"10.1073\/pnas.212290499","volume":"99","author":"Y Chen","year":"2002","unstructured":"Chen, Y., Chou, K., Fuchs, E., Havran, W. L. & Boismenu, R. Protection of the intestinal mucosa by intraepithelial \u03b3\u03b4 T cells. Proc. Natl Acad. Sci. USA 99, 14338\u201314343 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8090_CR8","doi-asserted-by":"publisher","first-page":"10261","DOI":"10.1073\/pnas.171320798","volume":"98","author":"AM Fahrer","year":"2001","unstructured":"Fahrer, A. M. et al. Attributes of \u03b3\u03b4 intraepithelial lymphocytes as suggested by their transcriptional profile. Proc. Natl Acad. Sci. USA 98, 10261\u201310266 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8090_CR9","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.cell.2009.09.033","volume":"139","author":"II Ivanov","year":"2009","unstructured":"Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485\u2013498 (2009).","journal-title":"Cell"},{"key":"BFncomms8090_CR10","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.immuni.2009.08.020","volume":"31","author":"V Gaboriau-Routhiau","year":"2009","unstructured":"Gaboriau-Routhiau, V. et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31, 677\u2013689 (2009).","journal-title":"Immunity"},{"key":"BFncomms8090_CR11","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nri2515","volume":"9","author":"JL Round","year":"2009","unstructured":"Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313\u2013323 (2009).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8090_CR12","doi-asserted-by":"publisher","first-page":"8743","DOI":"10.1073\/pnas.1019574108","volume":"108","author":"AS Ismail","year":"2011","unstructured":"Ismail, A. S. et al. \u03b3\u03b4 intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface. Proc. Natl Acad. Sci. USA 108, 8743\u20138748 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8090_CR13","doi-asserted-by":"publisher","first-page":"11774","DOI":"10.1073\/pnas.93.21.11774","volume":"93","author":"SJ Roberts","year":"1996","unstructured":"Roberts, S. J. et al. T-cell \u03b1\u03b2+ and \u03b3\u03b4+ deficient mice display abnormal but distinct phenotypes toward a natural, widespread infection of the intestinal epithelium. Proc. Natl Acad. Sci. USA 93, 11774\u201311779 (1996).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8090_CR14","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1046\/j.1365-2567.2000.00122.x","volume":"101","author":"AL Smith","year":"2000","unstructured":"Smith, A. L. & Hayday, A. C. An \u03b1\u03b2 T-cell-independent immunoprotective response towards gut coccidia is supported by \u03b3\u03b4 cells. Immunology 101, 325\u2013332 (2000).","journal-title":"Immunology"},{"key":"BFncomms8090_CR15","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1084\/jem.20030050","volume":"198","author":"E Ramsburg","year":"2003","unstructured":"Ramsburg, E., Tigelaar, R., Craft, J. & Hayday, A. Age-dependent requirement for \u03b3\u03b4 T cells in the primary but not secondary protective immune response against an intestinal parasite. J. Exp. Med. 198, 1403\u20131414 (2003).","journal-title":"J. Exp. Med."},{"key":"BFncomms8090_CR16","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/nri1394","volume":"4","author":"B Adkins","year":"2004","unstructured":"Adkins, B., Leclerc, C. & Marshall-Clarke, S. Neonatal adaptive immunity comes of age. Nat. Rev. Immunol. 4, 553\u2013564 (2004).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8090_CR17","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1203\/00006450-200104000-00017","volume":"49","author":"S Kuo","year":"2001","unstructured":"Kuo, S., Guindy, El, A., Panwala, C. M., Hagan, P. M. & Camerini, V. Differential appearance of T cell subsets in the large and small intestine of neonatal mice. Pediatr. Res. 49, 543\u2013551 (2001).","journal-title":"Pediatr. Res."},{"key":"BFncomms8090_CR18","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1111\/j.1365-2567.2006.02458.x","volume":"119","author":"AM Williams","year":"2006","unstructured":"Williams, A. M. et al. Effects of microflora on the neonatal development of gut mucosal T cells and myeloid cells in the mouse. Immunology 119, 470\u2013478 (2006).","journal-title":"Immunology"},{"key":"BFncomms8090_CR19","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1006\/cimm.1996.0023","volume":"167","author":"BC Sydora","year":"1996","unstructured":"Sydora, B. C., Jamieson, B. D., Ahmed, R. & Kronenberg, M. Intestinal intraepithelial lymphocytes respond to systemic lymphocytic choriomeningitis virus infection. Cell Immunol. 167, 161\u2013169 (1996).","journal-title":"Cell Immunol."},{"key":"BFncomms8090_CR20","first-page":"98","volume":"2","author":"SD London","year":"1989","unstructured":"London, S. D., Cebra, J. J. & Rubin, D. H. Intraepithelial lymphocytes contain virus-specific, MHC-restricted cytotoxic cell precursors after gut mucosal immunization with reovirus serotype 1\/Lang. Reg. Immunol. 2, 98\u2013102 (1989).","journal-title":"Reg. Immunol."},{"key":"BFncomms8090_CR21","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1128\/jvi.64.9.4375-4382.1990","volume":"64","author":"T Dharakul","year":"1990","unstructured":"Dharakul, T., Rott, L. & Greenberg, H. B. Recovery from chronic rotavirus infection in mice with severe combined immunodeficiency: virus clearance mediated by adoptive transfer of immune CD8+ T lymphocytes. J. Virol. 64, 4375\u20134382 (1990).","journal-title":"J. Virol."},{"key":"BFncomms8090_CR22","doi-asserted-by":"publisher","first-page":"1986","DOI":"10.4049\/jimmunol.164.4.1986","volume":"164","author":"S M\u00fcller","year":"2000","unstructured":"M\u00fcller, S., B\u00fchler-Jungo, M. & Mueller, C. Intestinal intraepithelial lymphocytes exert potent protective cytotoxic activity during an acute virus infection. J. Immunol. 164, 1986\u20131994 (2000).","journal-title":"J. Immunol."},{"key":"BFncomms8090_CR23","doi-asserted-by":"publisher","first-page":"4376","DOI":"10.1073\/pnas.1010647108","volume":"108","author":"A Bas","year":"2011","unstructured":"Bas, A. et al. Butyrophilin-like 1 encodes an enterocyte protein that selectively regulates functional interactions with T lymphocytes. Proc. Natl Acad. Sci. USA 108, 4376\u20134381 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8090_CR24","doi-asserted-by":"publisher","first-page":"15623","DOI":"10.1073\/pnas.95.26.15623","volume":"95","author":"SD Der","year":"1998","unstructured":"Der, S. D., Zhou, A., Williams, B. R. G. & Silverman, R. H. Identification of genes differentially regulated by interferon \u03b1, \u03b2, or \u03b3 using oligonucleotide arrays. Proc. Natl. Acad. Sci. USA 95, 15623\u201315628 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFncomms8090_CR25","doi-asserted-by":"publisher","first-page":"7749","DOI":"10.1128\/JVI.02438-06","volume":"81","author":"Z Zhou","year":"2007","unstructured":"Zhou, Z. et al. Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signaling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases. J. Virol. 81, 7749\u20137758 (2007).","journal-title":"J. Virol."},{"key":"BFncomms8090_CR26","doi-asserted-by":"publisher","first-page":"4239","DOI":"10.1073\/pnas.1114981109","volume":"109","author":"S-Y Liu","year":"2012","unstructured":"Liu, S.-Y., Sanchez, D. J., Aliyari, R., Lu, S. & Cheng, G. Systematic identification of type I and type II interferon-induced antiviral factors. Proc. Natl Acad. Sci. USA 109, 4239\u20134244 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8090_CR27","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1046\/j.1365-2443.2002.00515.x","volume":"7","author":"K Ogasawara","year":"2002","unstructured":"Ogasawara, K. et al. Requirement of the IFN-\u03b1\/\u03b2-induced CXCR3 chemokine signalling for CD8+ T cell activation. Genes Cells 7, 309\u2013320 (2002).","journal-title":"Genes Cells"},{"key":"BFncomms8090_CR28","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1038\/nature03464","volume":"434","author":"K Honda","year":"2005","unstructured":"Honda, K. et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434, 772\u2013777 (2005).","journal-title":"Nature"},{"key":"BFncomms8090_CR29","doi-asserted-by":"publisher","first-page":"3434","DOI":"10.4049\/jimmunol.179.6.3434","volume":"179","author":"PI Osterlund","year":"2007","unstructured":"Osterlund, P. I., Pietil\u00e4, T. E., Veckman, V., Kotenko, S. V. & Julkunen, I. IFN regulatory factor family members differentially regulate the expression of type III IFN (IFN-\u03bb) genes. J. Immunol. 179, 3434\u20133442 (2007).","journal-title":"J. Immunol."},{"key":"BFncomms8090_CR30","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.coviro.2011.11.001","volume":"1","author":"DE Levy","year":"2011","unstructured":"Levy, D. E., Mari\u00e9, I. J. & Durbin, J. E. Induction and function of type I and III interferon in response to viral infection. Curr. Opin. Virol. 1, 476\u2013486 (2011).","journal-title":"Curr. Opin. Virol."},{"key":"BFncomms8090_CR31","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1042\/BJ20101701","volume":"434","author":"K Clark","year":"2011","unstructured":"Clark, K. et al. Novel cross-talk within the IKK family controls innate immunity. Biochem. J. 434, 93\u2013104 (2011).","journal-title":"Biochem. J."},{"key":"BFncomms8090_CR32","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s00441-003-0706-4","volume":"313","author":"A Tamura","year":"2003","unstructured":"Tamura, A. et al. Distribution of two types of lymphocytes (intraepithelial and lamina-propria-associated) in the murine small intestine. Cell Tissue Res. 313, 47\u201353 (2003).","journal-title":"Cell Tissue Res."},{"key":"BFncomms8090_CR33","first-page":"R715","volume":"276","author":"N Radojevic","year":"1999","unstructured":"Radojevic, N. et al. Characterization of enteric functional changes evoked by in vivo anti-CD3 T cell activation. Am. J. Physiol. 276, R715\u2013R723 (1999).","journal-title":"Am. J. Physiol."},{"key":"BFncomms8090_CR34","first-page":"279","volume":"74","author":"P Garside","year":"1991","unstructured":"Garside, P., Felstein, M. V., Green, E. A. & Mowat, A. M. The role of interferon \u03b1\/\u03b2 in the induction of intestinal pathology in mice. Immunology 74, 279\u2013283 (1991).","journal-title":"Immunology"},{"key":"BFncomms8090_CR35","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1128\/JVI.01718-06","volume":"81","author":"I Koerner","year":"2007","unstructured":"Koerner, I., Kochs, G., Kalinke, U., Weiss, S. & Staeheli, P. Protective role of beta interferon in host defense against influenza A virus. J. Virol. 81, 2025\u20132030 (2007).","journal-title":"J. Virol."},{"key":"BFncomms8090_CR36","doi-asserted-by":"publisher","first-page":"e1000017","DOI":"10.1371\/journal.ppat.1000017","volume":"4","author":"C Sommereyns","year":"2008","unstructured":"Sommereyns, C., Paul, S., Staeheli, P. & Michiels, T. IFN-Lambda (IFN-\u03bb) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathog. 4, e1000017 (2008).","journal-title":"PLoS Pathog."},{"key":"BFncomms8090_CR37","doi-asserted-by":"publisher","first-page":"7776","DOI":"10.1128\/JVI.00546-06","volume":"81","author":"D Holzinger","year":"2007","unstructured":"Holzinger, D. et al. Induction of MxA gene expression by influenza A virus requires type I or type III interferon signaling. J. Virol. 81, 7776\u20137785 (2007).","journal-title":"J. Virol."},{"key":"BFncomms8090_CR38","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/S0014-5793(99)01598-7","volume":"463","author":"F Flohr","year":"1999","unstructured":"Flohr, F., Schneider-Schaulies, S., Haller, O. & Kochs, G. The central interactive region of human MxA GTPase is involved in GTPase activation and interaction with viral target structures. FEBS Lett. 463, 24\u201328 (1999).","journal-title":"FEBS Lett."},{"key":"BFncomms8090_CR39","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1126\/science.1077905","volume":"299","author":"SM Karst","year":"2003","unstructured":"Karst, S. M., Wobus, C. E., Lay, M., Davidson, J. & Virgin, H. W. STAT1-dependent innate immunity to a Norwalk-like virus. Science 299, 1575\u20131578 (2003).","journal-title":"Science"},{"key":"BFncomms8090_CR40","doi-asserted-by":"publisher","first-page":"5104","DOI":"10.1128\/JVI.02346-05","volume":"80","author":"CE Wobus","year":"2006","unstructured":"Wobus, C. E., Thackray, L. B. & Virgin, H. W. Murine norovirus: a model system to study norovirus biology and pathogenesis. J. Virol. 80, 5104\u20135112 (2006).","journal-title":"J. Virol."},{"key":"BFncomms8090_CR41","first-page":"247","volume":"56","author":"CC Hsu","year":"2006","unstructured":"Hsu, C. C., Riley, L. K., Wills, H. M. & Livingston, R. S. Persistent infection with and serologic cross-reactivity of three novel murine noroviruses. Comp. Med 56, 247\u2013251 (2006).","journal-title":"Comp. Med"},{"key":"BFncomms8090_CR42","doi-asserted-by":"publisher","first-page":"e432","DOI":"10.1371\/journal.pbio.0020432","volume":"2","author":"CE Wobus","year":"2004","unstructured":"Wobus, C. E. et al. Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. PLoS Biol. 2, e432 (2004).","journal-title":"PLoS Biol."},{"key":"BFncomms8090_CR43","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1126\/science.1258100","volume":"347","author":"TJ Nice","year":"2015","unstructured":"Nice, T. J. et al. Interferon-\u03bb cures persistent murine norovirus infection in the absence of adaptive immunity. Science 347, 269\u2013273 (2015).","journal-title":"Science"},{"key":"BFncomms8090_CR44","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1099\/vir.0.059188-0","volume":"95","author":"A Shortland","year":"2014","unstructured":"Shortland, A. et al. Pathology caused by persistent murine norovirus infection. J. Gen. Virol. 95, 413\u2013422 (2014).","journal-title":"J. Gen. Virol."},{"key":"BFncomms8090_CR45","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1126\/science.1254803","volume":"346","author":"S Ariotti","year":"2014","unstructured":"Ariotti, S. et al. T cell memory. Skin-resident memory CD8+ T cells trigger a state of tissue-wide pathogen alert. Science 346, 101\u2013105 (2014).","journal-title":"Science"},{"key":"BFncomms8090_CR46","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1126\/science.1254536","volume":"346","author":"JM Schenkel","year":"2014","unstructured":"Schenkel, J. M. et al. T cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science 346, 98\u2013101 (2014).","journal-title":"Science"},{"key":"BFncomms8090_CR47","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/ni.1718","volume":"10","author":"T Gebhardt","year":"2009","unstructured":"Gebhardt, T. et al. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat. Immunol. 10, 524\u2013530 (2009).","journal-title":"Nat. Immunol."},{"key":"BFncomms8090_CR48","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/ni.2568","volume":"14","author":"JM Schenkel","year":"2013","unstructured":"Schenkel, J. M., Fraser, K. A., Vezys, V. & Masopust, D. Sensing and alarm function of resident memory CD8+ T cells. Nat. Immunol. 14, 509\u2013513 (2013).","journal-title":"Nat. Immunol."},{"key":"BFncomms8090_CR49","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/mi.2012.96","volume":"6","author":"LS Cauley","year":"2012","unstructured":"Cauley, L. S. & LeFrancois, L. Guarding the perimeter: protection of the mucosa by tissue-resident memory T cells. Mucosal Immunol. 6, 14\u201323 (2012).","journal-title":"Mucosal Immunol."},{"key":"BFncomms8090_CR50","doi-asserted-by":"publisher","first-page":"19739","DOI":"10.1073\/pnas.1208927109","volume":"109","author":"S Ariotti","year":"2012","unstructured":"Ariotti, S. et al. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen. Proc. Natl Acad. Sci. USA 109, 19739\u201319744 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8090_CR51","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1126\/science.1211057","volume":"334","author":"SK Kuss","year":"2011","unstructured":"Kuss, S. K. et al. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 334, 249\u2013252 (2011).","journal-title":"Science"},{"key":"BFncomms8090_CR52","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1126\/science.1210718","volume":"334","author":"M Kane","year":"2011","unstructured":"Kane, M. et al. Successful transmission of a retrovirus depends on the commensal microbiota. Science 334, 245\u2013249 (2011).","journal-title":"Science"},{"key":"BFncomms8090_CR53","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/nri2144","volume":"7","author":"RA Eagle","year":"2007","unstructured":"Eagle, R. A. & Trowsdale, J. Promiscuity and the single receptor: NKG2D. Nat. Rev. Immunol. 7, 737\u2013744 (2007).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8090_CR54","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.1128\/IAI.66.12.5677-5683.1998","volume":"66","author":"K Hirose","year":"1998","unstructured":"Hirose, K. et al. Interleukin-15 may be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in rats. Infect. Immun. 66, 5677\u20135683 (1998).","journal-title":"Infect. Immun."},{"key":"BFncomms8090_CR55","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1111\/j.1365-2249.2004.02431.x","volume":"136","author":"A Okazawa","year":"2004","unstructured":"Okazawa, A. et al. Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes. Clin. Exp. Immunol. 136, 269\u2013276 (2004).","journal-title":"Clin. Exp. Immunol."},{"key":"BFncomms8090_CR56","doi-asserted-by":"publisher","first-page":"4176","DOI":"10.4049\/jimmunol.172.7.4176","volume":"172","author":"L Saurer","year":"2004","unstructured":"Saurer, L. et al. Virus-induced activation of self-specific TCR\u03b1\u03b2 CD8\u03b1\u03b1 intraepithelial lymphocytes does not abolish their self-tolerance in the intestine. J. Immunol. 172, 4176\u20134183 (2004).","journal-title":"J. Immunol."},{"key":"BFncomms8090_CR57","doi-asserted-by":"publisher","first-page":"6147","DOI":"10.1073\/pnas.92.13.6147","volume":"92","author":"H Komano","year":"1995","unstructured":"Komano, H. et al. Homeostatic regulation of intestinal epithelia by intraepithelial \u03b3\u03b4 T cells. Proc. Natl Acad. Sci. USA 92, 6147\u20136151 (1995).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8090_CR58","doi-asserted-by":"publisher","first-page":"7576","DOI":"10.1074\/jbc.M608618200","volume":"282","author":"K Onoguchi","year":"2007","unstructured":"Onoguchi, K. et al. Viral infections activate types I and III interferon genes through a common mechanism. J. Biol. Chem. 282, 7576\u20137581 (2007).","journal-title":"J. Biol. Chem."},{"key":"BFncomms8090_CR59","doi-asserted-by":"publisher","first-page":"5888","DOI":"10.4049\/jimmunol.0902314","volume":"185","author":"AHH van Boxel-Dezaire","year":"2010","unstructured":"van Boxel-Dezaire, A. H. H. et al. Major differences in the responses of primary human leukocyte subsets to IFN-\u03b2. J. Immunol. 185, 5888\u20135899 (2010).","journal-title":"J. Immunol."},{"key":"BFncomms8090_CR60","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/35073080","volume":"2","author":"T Taniguchi","year":"2001","unstructured":"Taniguchi, T. & Takaoka, A. A weak signal for strong responses: interferon-\u03b1\/\u03b2 revisited. Nat. Rev. Mol. Cell. Biol. 2, 378 (2001).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"BFncomms8090_CR61","doi-asserted-by":"publisher","first-page":"7944","DOI":"10.1073\/pnas.1100552108","volume":"108","author":"J Pott","year":"2011","unstructured":"Pott, J. et al. IFN-\u03bb determines the intestinal epithelial antiviral host defense. Proc. Natl Acad. Sci. USA 108, 7944\u20137949 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8090_CR62","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1016\/j.cell.2010.02.034","volume":"140","author":"GS Hotamisligil","year":"2010","unstructured":"Hotamisligil, G. S. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140, 900\u2013917 (2010).","journal-title":"Cell"},{"key":"BFncomms8090_CR63","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.it.2004.08.010","volume":"25","author":"JD MacMicking","year":"2004","unstructured":"MacMicking, J. D. IFN-inducible GTPases and immunity to intracellular pathogens. Trends Immunol. 25, 601\u2013609 (2004).","journal-title":"Trends Immunol."},{"key":"BFncomms8090_CR64","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/mi.2008.62","volume":"2","author":"M Schnoor","year":"2009","unstructured":"Schnoor, M., Betanzos, A., Weber, D. A. & Parkos, C. A. Guanylate-binding protein-1 is expressed at tight junctions of intestinal epithelial cells in response to interferon-gamma and regulates barrier function through effects on apoptosis. Mucosal Immunol. 2, 33\u201342 (2009).","journal-title":"Mucosal Immunol."},{"key":"BFncomms8090_CR65","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/S0140-6736(04)15641-9","volume":"363","author":"B Lopman","year":"2004","unstructured":"Lopman, B. et al. Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant. Lancet 363, 682\u2013688 (2004).","journal-title":"Lancet"},{"key":"BFncomms8090_CR66","first-page":"1347","volume":"17","author":"SS Monroe","year":"2011","unstructured":"Monroe, S. S. Control and prevention of viral gastroenteritis. Emerging Infect. Dis 17, 1347\u20131348 (2011).","journal-title":"Emerging Infect. Dis"},{"key":"BFncomms8090_CR67","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0022-1759(93)90329-6","volume":"166","author":"K Vidal","year":"1993","unstructured":"Vidal, K., Grosjean, I., Revillard, J. P., Gespach, C. & Kaiserlian, D. Immortalization of mouse intestinal epithelial cells by the SV40-large T gene. Phenotypic and immune characterization of the MODE-K cell line. J. Immunol. Methods 166, 63\u201373 (1993).","journal-title":"J. Immunol. Methods"},{"key":"BFncomms8090_CR68","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1038\/ni736","volume":"2","author":"C Asselin-Paturel","year":"2001","unstructured":"Asselin-Paturel, C. et al. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat. Immunol. 2, 1144\u20131150 (2001).","journal-title":"Nat. Immunol."},{"key":"BFncomms8090_CR69","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0165-5728(90)90073-V","volume":"27","author":"E Blasi","year":"1990","unstructured":"Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R. & Bistoni, F. Immortalization of murine microglial cells by a v-raf\/v-myc carrying retrovirus. J. Neuroimmunol. 27, 229\u2013237 (1990).","journal-title":"J. Neuroimmunol."},{"key":"BFncomms8090_CR70","first-page":"493","volume":"27","author":"LJ Reed","year":"1938","unstructured":"Reed, L. J. & Muench, H. A simple and reliable method of estimating fifty per cent end points. Am. J. Hyg. 27, 493\u2013497 (1938).","journal-title":"Am. J. Hyg."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms8090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms8090","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms8090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T11:35:53Z","timestamp":1672918553000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms8090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,19]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,11,3]]}},"alternative-id":["BFncomms8090"],"URL":"https:\/\/doi.org\/10.1038\/ncomms8090","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,19]]},"assertion":[{"value":"12 September 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7090"}}