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dc.contributor.authorAden, Konrad
dc.contributor.authorTran, Florian
dc.contributor.authorIto, Go
dc.contributor.authorSheibani-Tezerji, Raheleh
dc.contributor.authorLipinski, Simone
dc.contributor.authorKuiper, Jan W
dc.contributor.authorTschurtschenthaler, Markus
dc.contributor.authorSaveljeva, Svetlana
dc.contributor.authorBhattacharyya, Joya
dc.contributor.authorHäsler, Robert
dc.contributor.authorBartsch, Kareen
dc.contributor.authorLuzius, Anne
dc.contributor.authorJentzsch, Marlene
dc.contributor.authorFalk-Paulsen, Maren
dc.contributor.authorStengel, Stephanie T
dc.contributor.authorWelz, Lina
dc.contributor.authorSchwarzer, Robin
dc.contributor.authorRabe, Björn
dc.contributor.authorBarchet, Winfried
dc.contributor.authorKrautwald, Stefan
dc.contributor.authorHartmann, Gunther
dc.contributor.authorPasparakis, Manolis
dc.contributor.authorBlumberg, Richard S
dc.contributor.authorSchreiber, Stefan
dc.contributor.authorKaser, Arthur
dc.contributor.authorRosenstiel, Philip
dc.date.accessioned2018-09-08T06:32:51Z
dc.date.available2018-09-08T06:32:51Z
dc.date.issued2018-11-05
dc.identifier.issn0022-1007
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279862
dc.description.abstractA coding variant of the inflammatory bowel disease (IBD) risk gene ATG16L1 has been associated with defective autophagy and deregulation of endoplasmic reticulum (ER) function. IL-22 is a barrier protective cytokine by inducing regeneration and antimicrobial responses in the intestinal mucosa. We show that ATG16L1 critically orchestrates IL-22 signaling in the intestinal epithelium. IL-22 stimulation physiologically leads to transient ER stress and subsequent activation of STING-dependent type I interferon (IFN-I) signaling, which is augmented in Atg16l1 ΔIEC intestinal organoids. IFN-I signals amplify epithelial TNF production downstream of IL-22 and contribute to necroptotic cell death. In vivo, IL-22 treatment in Atg16l1 ΔIEC and Atg16l1 ΔIEC/Xbp1 ΔIEC mice potentiates endogenous ileal inflammation and causes widespread necroptotic epithelial cell death. Therapeutic blockade of IFN-I signaling ameliorates IL-22-induced ileal inflammation in Atg16l1 ΔIEC mice. Our data demonstrate an unexpected role of ATG16L1 in coordinating the outcome of IL-22 signaling in the intestinal epithelium.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherRockefeller University Press
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectIntestinal Mucosa
dc.subjectCaco-2 Cells
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectHumans
dc.subjectMice
dc.subjectInflammatory Bowel Diseases
dc.subjectNucleotidyltransferases
dc.subjectCarrier Proteins
dc.subjectSignal Transduction
dc.subjectGenetic Variation
dc.subjectAutophagy-Related Proteins
dc.subjectInterleukins
dc.subjectMembrane Proteins
dc.titleATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING.
dc.typeArticle
prism.endingPage2886
prism.issueIdentifier11
prism.publicationDate2018
prism.publicationNameJ Exp Med
prism.startingPage2868
prism.volume215
dc.identifier.doi10.17863/CAM.27230
dcterms.dateAccepted2018-08-20
rioxxterms.versionofrecord10.1084/jem.20171029
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-11
dc.contributor.orcidTran, Florian [0000-0002-3735-9872]
dc.contributor.orcidLipinski, Simone [0000-0002-9322-7372]
dc.contributor.orcidTschurtschenthaler, Markus [0000-0002-0060-4790]
dc.contributor.orcidBhattacharyya, Joya [0000-0003-1745-4167]
dc.contributor.orcidKrautwald, Stefan [0000-0001-7768-2132]
dc.contributor.orcidBlumberg, Richard S [0000-0002-9704-248X]
dc.contributor.orcidKaser, Arthur [0000-0003-1419-3344]
dc.contributor.orcidRosenstiel, Philip [0000-0002-9692-8828]
dc.identifier.eissn1540-9538
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEuropean Research Council (260961)
pubs.funder-project-idWellcome Trust (106260/Z/14/Z)
pubs.funder-project-idEuropean Research Council (648889)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (733100)
cam.issuedOnline2018-09-25
cam.orpheus.successThu Jan 30 10:54:30 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International