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dc.contributor.authorGrootjans, Joepen
dc.contributor.authorKrupka, Niklasen
dc.contributor.authorHosomi, Shuheien
dc.contributor.authorMatute, Juan Den
dc.contributor.authorHanley, Thomasen
dc.contributor.authorSaveljeva, Svetlanaen
dc.contributor.authorGensollen, Thomasen
dc.contributor.authorHeijmans, Jaromen
dc.contributor.authorLi, Haien
dc.contributor.authorLimenitakis, Julien Pen
dc.contributor.authorGanal-Vonarburg, Stephanie Cen
dc.contributor.authorSuo, Shengbaoen
dc.contributor.authorLuoma, Adrienne Men
dc.contributor.authorShimodaira, Yosukeen
dc.contributor.authorDuan, Jinzhien
dc.contributor.authorShih, David Qen
dc.contributor.authorConner, Margaret Een
dc.contributor.authorGlickman, Jonathan Nen
dc.contributor.authorFuhler, Gwenny Men
dc.contributor.authorPalm, Noah Wen
dc.contributor.authorde Zoete, Marcel Ren
dc.contributor.authorvan der Woude, C Jannekeen
dc.contributor.authorYuan, Guo-Chengen
dc.contributor.authorWucherpfennig, Kai Wen
dc.contributor.authorTargan, Stephan Ren
dc.contributor.authorRosenstiel, Philipen
dc.contributor.authorFlavell, Richard Aen
dc.contributor.authorMcCoy, Kathy Den
dc.contributor.authorMacpherson, Andrew Jen
dc.contributor.authorKaser, Arthuren
dc.contributor.authorBlumberg, Richard Sen
dc.date.accessioned2019-02-16T00:31:30Z
dc.date.available2019-02-16T00:31:30Z
dc.date.issued2019-03en
dc.identifier.issn0036-8075
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/289544
dc.description.abstractImmunoglobulin A (IgA) is the major secretory immunoglobulin isotype at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased LP and luminal IgA. Increased numbers of IgA-producing plasma cells are observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that produce a barrier-protective TI IgA response.
dc.description.sponsorshipWellcome Trust Senior Investigator Award 106260/Z/14/Z HORIZON2020/European Research Council Consolidator Grant 648889
dc.format.mediumPrinten
dc.languageengen
dc.subjectIntestinal Mucosaen
dc.subjectPlasma Cellsen
dc.subjectEpithelial Cellsen
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectMice, Knockouten
dc.subjectHumansen
dc.subjectMiceen
dc.subjectInflammationen
dc.subjectImmunoglobulin Aen
dc.subjectTissue Culture Techniquesen
dc.subjectImmunity, Mucosalen
dc.subjectAutophagyen
dc.subjectEndoplasmic Reticulum Stressen
dc.subjectX-Box Binding Protein 1en
dc.subjectAutophagy-Related Proteinsen
dc.titleEpithelial endoplasmic reticulum stress orchestrates a protective IgA response.en
dc.typeArticle
prism.endingPage998
prism.issueIdentifier6430en
prism.publicationDate2019en
prism.publicationNameScience (New York, N.Y.)en
prism.startingPage993
prism.volume363en
dc.identifier.doi10.17863/CAM.36794
dcterms.dateAccepted2019-02-08en
rioxxterms.versionofrecord10.1126/science.aat7186en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-03en
dc.contributor.orcidGrootjans, Joep [0000-0002-2805-4831]
dc.contributor.orcidKrupka, Niklas [0000-0001-5948-7536]
dc.contributor.orcidHosomi, Shuhei [0000-0002-8808-5672]
dc.contributor.orcidMatute, Juan D [0000-0002-1703-8115]
dc.contributor.orcidHanley, Thomas [0000-0002-4270-8299]
dc.contributor.orcidSaveljeva, Svetlana [0000-0002-0644-9752]
dc.contributor.orcidGensollen, Thomas [0000-0002-9834-5490]
dc.contributor.orcidHeijmans, Jarom [0000-0001-9615-7851]
dc.contributor.orcidLi, Hai [0000-0002-4762-9362]
dc.contributor.orcidLimenitakis, Julien P [0000-0002-6785-3492]
dc.contributor.orcidGanal-Vonarburg, Stephanie C [0000-0002-2548-7754]
dc.contributor.orcidShimodaira, Yosuke [0000-0003-0314-9196]
dc.contributor.orcidDuan, Jinzhi [0000-0001-9351-4956]
dc.contributor.orcidShih, David Q [0000-0003-1335-7044]
dc.contributor.orcidConner, Margaret E [0000-0002-7146-8159]
dc.contributor.orcidGlickman, Jonathan N [0000-0003-0910-2655]
dc.contributor.orcidPalm, Noah W [0000-0001-7262-9455]
dc.contributor.orcidvan der Woude, C Janneke [0000-0003-3875-6957]
dc.contributor.orcidWucherpfennig, Kai W [0000-0002-1829-302X]
dc.contributor.orcidRosenstiel, Philip [0000-0002-9692-8828]
dc.contributor.orcidFlavell, Richard A [0000-0003-4461-0778]
dc.contributor.orcidMcCoy, Kathy D [0000-0002-3900-9227]
dc.contributor.orcidMacpherson, Andrew J [0000-0002-7192-0184]
dc.contributor.orcidKaser, Arthur [0000-0003-1419-3344]
dc.contributor.orcidBlumberg, Richard S [0000-0002-9704-248X]
dc.identifier.eissn1095-9203
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEvelyn Trust (13/27)
pubs.funder-project-idWELLCOME TRUST (106260/Z/14/Z)
pubs.funder-project-idECH2020 EUROPEAN RESEARCH COUNCIL (ERC) (648889)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (BRC)
cam.orpheus.successThu Jan 30 10:50:49 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2019-03-31


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