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dc.contributor.authorHosomi, Shuheien
dc.contributor.authorGrootjans, Joepen
dc.contributor.authorTschurtschenthaler, Markusen
dc.contributor.authorKrupka, Niklasen
dc.contributor.authorMatute, Juan Den
dc.contributor.authorFlak, Magdalena Ben
dc.contributor.authorMartinez-Naves, Eduardoen
dc.contributor.authorGomez Del Moral, Manuelen
dc.contributor.authorGlickman, Jonathan Nen
dc.contributor.authorOhira, Mizukien
dc.contributor.authorLanier, Lewis Len
dc.contributor.authorKaser, Arthuren
dc.contributor.authorBlumberg, Richarden
dc.date.accessioned2017-12-12T16:04:21Z
dc.date.available2017-12-12T16:04:21Z
dc.date.issued2017-10en
dc.identifier.issn0022-1007
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/270164
dc.description.abstractEndoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IEC) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box binding protein-1 (Xbp1), an unfolded protein response (UPR)-related transcription factor. Here, Xbp1 deletion in the epithelium (Xbp1ΔIEC) is shown to cause increased expression of natural-killer group 2 member D (NKG2D) ligand (NKG2DL) murine UL16-binding protein like transcript 1 (MULT1) and its human orthologue cytomegalovirus UL16-binding protein (ULBP) via ER stress-related transcription factor C/EBP homology protein (CHOP). Increased NKG2DL expression on mouse IECs is associated with increased numbers of intraepithelial NKG2D-expressing group 1 ILCs. Blockade of NKG2D suppresses cytolysis against ER-stressed epithelial cells in vitro and spontaneous enteritis in vivo. Pharmacological depletion of NK1.1+ cells also significantly improved enteritis, while enteritis was not ameliorated in recombinase activating gene 1 (Rag1)–/–;Xbp1ΔIEC mice. These studies reveal innate immune sensing of ER stress in IEC as an important mechanism of intestinal inflammation.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherRockefeller University Press
dc.subjectIntestinal Mucosaen
dc.subjectEndoplasmic Reticulumen
dc.subjectAnimalsen
dc.subjectMice, Inbred BALB Cen
dc.subjectMice, Transgenicen
dc.subjectMiceen
dc.subjectEnteritisen
dc.subjectInflammationen
dc.subjectCarrier Proteinsen
dc.subjectMembrane Proteinsen
dc.subjectHistocompatibility Antigens Class Ien
dc.subjectUp-Regulationen
dc.subjectGene Deletionen
dc.subjectStress, Physiologicalen
dc.subjectNK Cell Lectin-Like Receptor Subfamily Ken
dc.subjectX-Box Binding Protein 1en
dc.titleIntestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation.en
dc.typeArticle
prism.endingPage2997
prism.issueIdentifier10en
prism.publicationDate2017en
prism.publicationNameThe Journal of experimental medicineen
prism.startingPage2985
prism.volume214en
dc.identifier.doi10.17863/CAM.16998
dcterms.dateAccepted2017-07-10en
rioxxterms.versionofrecord10.1084/jem.20162041en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-10en
dc.contributor.orcidTschurtschenthaler, Markus [0000-0002-0060-4790]
dc.contributor.orcidKrupka, Niklas [0000-0001-5948-7536]
dc.contributor.orcidFlak, Magdalena B [0000-0002-8238-9835]
dc.contributor.orcidLanier, Lewis L [0000-0003-1308-3952]
dc.contributor.orcidKaser, Arthur [0000-0003-1419-3344]
dc.contributor.orcidBlumberg, Richard [0000-0002-9704-248X]
dc.identifier.eissn1540-9538
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idECH2020 EUROPEAN RESEARCH COUNCIL (ERC) (648889)
rioxxterms.freetoread.startdate2018-07-26


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