Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/99676
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DC Field | Value | Language |
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dc.contributor.author | Koyama, M. | - |
dc.contributor.author | Cheong, M. | - |
dc.contributor.author | Markey, K. | - |
dc.contributor.author | Gartlan, K. | - |
dc.contributor.author | Kuns, R. | - |
dc.contributor.author | Locke, K. | - |
dc.contributor.author | Lineburg, K. | - |
dc.contributor.author | Teal, B. | - |
dc.contributor.author | Leveque-El mouttie, L. | - |
dc.contributor.author | Bunting, M. | - |
dc.contributor.author | Vuckovic, S. | - |
dc.contributor.author | Zhang, P. | - |
dc.contributor.author | Teng, M. | - |
dc.contributor.author | Varelias, A. | - |
dc.contributor.author | Tey, S. | - |
dc.contributor.author | Wockner, L. | - |
dc.contributor.author | Engwerda, C. | - |
dc.contributor.author | Smyth, M. | - |
dc.contributor.author | Belz, G. | - |
dc.contributor.author | McColl, S. | - |
dc.contributor.author | et al. | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Journal of Experimental Medicine, 2015; 212(8):1303-1321 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.issn | 1540-9538 | - |
dc.identifier.uri | http://hdl.handle.net/2440/99676 | - |
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.statementofresponsibility | Motoko Koyama, Melody Cheong, Kate A. Markey, Kate H. Gartlan, Rachel D. Kuns, Kelly R. Locke, Katie E. Lineburg, Bianca E. Teal, Lucie Leveque-El mouttie, Mark D. Bunting, Slavica Vuckovic, Ping Zhang, Michele W.L. Teng, Antiopi Varelias, Siok-Keen Tey, Leesa F. Wockner, Christian R. Engwerda, Mark J. Smyth, Gabrielle T. Belz, Shaun R. McColl, Kelli P.A. MacDonald, and Geoffrey R. Hill | - |
dc.language.iso | en | - |
dc.publisher | Rockefeller University Press | - |
dc.rights | © 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/). | - |
dc.source.uri | http://dx.doi.org/10.1084/jem.20150329 | - |
dc.subject | Dendritic Cells | - |
dc.subject | T-Lymphocytes | - |
dc.subject | Advanced Glycosylation End Product-Specific Receptor | - |
dc.title | Donor colonic CD103⁺ dendritic cells determine the severity of acute graft-versus-host disease | - |
dc.title.alternative | Donor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1084/jem.20150329 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Bunting, M. [0000-0002-7575-4910] | - |
dc.identifier.orcid | McColl, S. [0000-0003-0949-4660] | - |
Appears in Collections: | Aurora harvest 3 IPAS publications |
Files in This Item:
File | Description | Size | Format | |
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hdl_99676.pdf | Published version | 5.89 MB | Adobe PDF | View/Open |
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