Show simple item record

dc.contributor.authorKoyama, Motoko
dc.contributor.authorCheong, Melody
dc.contributor.authorMarkey, Kate A
dc.contributor.authorGartlan, Kate H
dc.contributor.authorKuns, Rachel D
dc.contributor.authorLocke, Kelly R
dc.contributor.authorLineburg, Katie E
dc.contributor.authorTeal, Bianca E
dc.contributor.authorLeveque-El Mouttie, Lucie
dc.contributor.authorBunting, Mark D
dc.contributor.authorVuckovic, Slavica
dc.contributor.authorZhang, Ping
dc.contributor.authorTeng, Michele WL
dc.contributor.authorVarelias, Antiopi
dc.contributor.authorEngwerda, Christian R.
dc.contributor.authoret al.
dc.date.accessioned2021-01-15T05:04:54Z
dc.date.available2021-01-15T05:04:54Z
dc.date.issued2015
dc.identifier.issn0022-1007
dc.identifier.doi10.1084/jem.20150329
dc.identifier.urihttp://hdl.handle.net/10072/401157
dc.description.abstractThe primacy of the gastrointestinal (GI) tract in dictating the outcome of graft-versus-host disease (GVHD) is broadly accepted; however, the mechanisms controlling this effect are poorly understood. Here, we demonstrate that GVHD markedly enhances alloantigen presentation within the mesenteric lymph nodes (mLNs), mediated by donor CD103(+)CD11b(-) dendritic cells (DCs) that migrate from the colon under the influence of CCR7. Expansion and differentiation of donor T cells specifically within the mLNs is driven by profound levels of alloantigen, IL-12, and IL-6 promoted by Toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signals. Critically, alloantigen presentation in the mLNs imprints gut-homing integrin signatures on donor T cells, leading to their emigration into the GI tract where they mediate fulminant disease. These data identify a critical, anatomically distinct, donor DC subset that amplifies GVHD. We thus highlight multiple therapeutic targets and the ability of GVHD, once initiated by recipient antigen-presenting cells, to generate a profound, localized, and lethal feed-forward cascade of donor DC-mediated indirect alloantigen presentation and cytokine secretion within the GI tract.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherRockefeller University Press
dc.relation.ispartofpagefrom1303
dc.relation.ispartofpageto1321
dc.relation.ispartofissue8
dc.relation.ispartofjournalJournal of Experimental Medicine
dc.relation.ispartofvolume212
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode32
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsImmunology
dc.subject.keywordsMedicine, Research & Experimental
dc.subject.keywordsResearch & Experimental Medicine
dc.titleDonor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationKoyama, M; Cheong, M; Markey, KA; Gartlan, KH; Kuns, RD; Locke, KR; Lineburg, KE; Teal, BE; Leveque-El Mouttie, L; Bunting, MD; Vuckovic, S; Zhang, P; Teng, MWL; Varelias, A; et al., Donor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease, Journal of Experimental Medicine, 2015, 212 (8), pp. 1303-1321
dcterms.dateAccepted2015-06-26
dcterms.licensehttp://creativecommons.org/licenses/by-nc-sa/3.0
dc.date.updated2021-01-15T04:51:37Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2015 Koyama et al. This article is distributed under the terms of an Attribution– Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial– Share Alike 3.0 Unported license, as described at http://creativecommons.org/ licenses/by-nc-sa/3.0/).
gro.hasfulltextFull Text
gro.griffith.authorEngwerda, Christian R.


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record