dc.contributor.author | Koyama, Motoko | |
dc.contributor.author | Cheong, Melody | |
dc.contributor.author | Markey, Kate A | |
dc.contributor.author | Gartlan, Kate H | |
dc.contributor.author | Kuns, Rachel D | |
dc.contributor.author | Locke, Kelly R | |
dc.contributor.author | Lineburg, Katie E | |
dc.contributor.author | Teal, Bianca E | |
dc.contributor.author | Leveque-El Mouttie, Lucie | |
dc.contributor.author | Bunting, Mark D | |
dc.contributor.author | Vuckovic, Slavica | |
dc.contributor.author | Zhang, Ping | |
dc.contributor.author | Teng, Michele WL | |
dc.contributor.author | Varelias, Antiopi | |
dc.contributor.author | Engwerda, Christian R. | |
dc.contributor.author | et al. | |
dc.date.accessioned | 2021-01-15T05:04:54Z | |
dc.date.available | 2021-01-15T05:04:54Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 0022-1007 | |
dc.identifier.doi | 10.1084/jem.20150329 | |
dc.identifier.uri | http://hdl.handle.net/10072/401157 | |
dc.description.abstract | The 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.peerreviewed | Yes | |
dc.language | English | |
dc.publisher | Rockefeller University Press | |
dc.relation.ispartofpagefrom | 1303 | |
dc.relation.ispartofpageto | 1321 | |
dc.relation.ispartofissue | 8 | |
dc.relation.ispartofjournal | Journal of Experimental Medicine | |
dc.relation.ispartofvolume | 212 | |
dc.subject.fieldofresearch | Biomedical and clinical sciences | |
dc.subject.fieldofresearchcode | 32 | |
dc.subject.keywords | Science & Technology | |
dc.subject.keywords | Life Sciences & Biomedicine | |
dc.subject.keywords | Immunology | |
dc.subject.keywords | Medicine, Research & Experimental | |
dc.subject.keywords | Research & Experimental Medicine | |
dc.title | Donor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Koyama, 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.dateAccepted | 2015-06-26 | |
dcterms.license | http://creativecommons.org/licenses/by-nc-sa/3.0 | |
dc.date.updated | 2021-01-15T04:51:37Z | |
dc.description.version | Version 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.hasfulltext | Full Text | |
gro.griffith.author | Engwerda, Christian R. | |