Show simple item record

dc.contributor.authorElder, Matthew Jen
dc.contributor.authorWebster, Stevenen
dc.contributor.authorWilliams, David Len
dc.contributor.authorGaston, Hillen
dc.contributor.authorGoodall, Janeen
dc.date.accessioned2016-01-13T18:56:50Z
dc.date.available2016-01-13T18:56:50Z
dc.date.issued2015-12-02en
dc.identifier.citationElder et al. European Journal of Immunology (2016), 46(2), pp. 455–463. doi: 10.1002/eji.201545537en
dc.identifier.issn0014-2980
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253252
dc.description.abstractThymic stromal lymphopoietin (TSLP) produced by epithelial cells acts on dendritic cells (DCs) to drive differentiation of TH2-cells, and is therefore important in allergic disease pathogenesis. However, DCs themselves make significant amounts of TSLP in response to microbial products, but little is known about the key downstream signals that induce and modulate this TSLP secretion from human DCs. We show that human monocyte derived DC (mDC) secretion of TSLP in response to Candida albicans and β-glucans requires dectin-1, Syk, NF-κB, and p38 MAPK signaling. In addition, TSLP production by mDCs is greatly enhanced by IL-1β, but not TNF-α, in contrast to epithelial cells. Furthermore, TSLP secretion is significantly increased by signals emanating from the endoplasmic reticulum (ER) stress response, specifically the unfolded protein response sensors, inositol-requiring transmembrane kinase/endonuclease 1 and protein kinase R-like ER kinase, which are activated by dectin-1 stimulation. Thus, TSLP production by mDCs requires the integration of signals from dectin-1, the IL-1 receptor, and ER stress signaling pathways. Autocrine TSLP production is likely to play a role in mDC-controlled immune responses at sites removed from epithelial cell production of the cytokine, such as lymphoid tissue.
dc.description.sponsorshipThis research was supported by Arthritis Research UK and the Cambridge NIHR BRC Cell Phenotyping Hub. This research was also supported, in part, by NIH GM53522 and GM083016 to D.L.W.
dc.languageEnglishen
dc.language.isoenen
dc.publisherWiley
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectdectin-1en
dc.subjectER stressen
dc.subjectIL-1βen
dc.subjectTSLPen
dc.titleTSLP production by dendritic cells is modulated by IL-1β and components of the endoplasmic reticulum stress responseen
dc.typeArticle
dc.description.versionThis is the final version of the article. It was first available from Wiley via http://dx.doi.org/10.1002/eji.201545537en
prism.endingPage463
prism.publicationDate2015en
prism.publicationNameEuropean Journal of Immunologyen
prism.startingPage455
prism.volume46en
dcterms.dateAccepted2015-11-09en
rioxxterms.versionofrecord10.1002/eji.201545537en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-12-02en
dc.contributor.orcidWebster, Steven [0000-0002-0864-1182]
dc.contributor.orcidGaston, Hill [0000-0002-5789-5111]
dc.contributor.orcidGoodall, Jane [0000-0002-3761-161X]
dc.identifier.eissn1521-4141
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idArthritis Research Uk (19639)
pubs.funder-project-idMRC (G1001765)
pubs.funder-project-idArthritis Research Uk (19962)


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales