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dc.contributor.authorFergusson, Joannah Ren
dc.contributor.authorMorgan, Michaelen
dc.contributor.authorBruchard, Melanieen
dc.contributor.authorHuitema, Leonieen
dc.contributor.authorHeesters, Balthasar Aen
dc.contributor.authorvan Unen, Vincenten
dc.contributor.authorvan Hamburg, Jan Pieten
dc.contributor.authorvan der Wel, Nicole Nen
dc.contributor.authorPicavet, Daisyen
dc.contributor.authorKoning, Fritsen
dc.contributor.authorTas, Sander Wen
dc.contributor.authorAnderson, Mark Sen
dc.contributor.authorMarioni, Johnen
dc.contributor.authorHolländer, Georg Aen
dc.contributor.authorSpits, Hergenen
dc.date.accessioned2019-04-05T23:30:12Z
dc.date.available2019-04-05T23:30:12Z
dc.identifier.issn1664-3224
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/291178
dc.description.abstractExpression of the Autoimmune regulator (AIRE) outside of the thymus has long been suggested in both humans and mice, but the cellular source in humans has remained undefined. Here we identify AIRE expression in human tonsils and extensively analyzed these "extra-thymic AIRE expressing cells" (eTACs) using combinations of flow cytometry, CyTOF and single cell RNA-sequencing. We identified AIRE+ cells as dendritic cells (DCs) with a mature and migratory phenotype including high levels of antigen presenting molecules and costimulatory molecules, and specific expression of CD127, CCR7, and PDL1. These cells also possessed the ability to stimulate and re-stimulate T cells and displayed reduced responses to toll-like receptor (TLR) agonists compared to conventional DCs. While expression of AIRE was enriched within CCR7+CD127+ DCs, single-cell RNA sequencing revealed expression of AIRE to be transient, rather than stable, and associated with the differentiation to a mature phenotype. The role of AIRE in central tolerance induction within the thymus is well-established, however our study shows that AIRE expression within the periphery is not associated with an enriched expression of tissue-restricted antigens (TRAs). This unexpected finding, suggestive of wider functions of AIRE, may provide an explanation for the non-autoimmune symptoms of APECED patients who lack functional AIRE.
dc.description.sponsorshipJF and HS were funded by project ERC-2013-ADG number 341038. MB was funded by EMBO ALTF 786-2013. BH was supported by the Netherlands Organization for Scientific Research (NWO) Veni program (91618032). LH, JpvH, and ST were supported by a grant from the Dutch Arthritis Foundation (2013_2_37). MM was supported by Wellcome Trust (grant105045/Z/14/Z). JM was supported by core funding from the European Molecular Biology Laboratory and from Cancer Research UK (award number 17197).
dc.languageengen
dc.publisherFrontiers Media
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAIREen
dc.subjectPDL1en
dc.subjectdendritic cellsen
dc.subjectmaturationen
dc.subjecttissue restricted antigenen
dc.titleMaturing Human CD127+ CCR7+ PDL1+ Dendritic Cells Express AIRE in the Absence of Tissue Restricted Antigens.en
dc.typeArticle
prism.number2902en
prism.publicationNameFrontiers in Immunologyen
prism.volume9en
dc.identifier.doi10.17863/CAM.38358
dcterms.dateAccepted2018-11-27en
rioxxterms.versionofrecord10.3389/fimmu.2018.02902en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-11-27en
dc.contributor.orcidMorgan, Michael [0000-0003-0757-0711]
dc.contributor.orcidMarioni, John [0000-0001-9092-0852]
dc.identifier.eissn1664-3224
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (C14303_do not transfer)
cam.issuedOnline2019-01-14en
dc.identifier.urlhttps://www.frontiersin.org/articles/10.3389/fimmu.2018.02902/fullen


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