Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/99676
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Type: | Journal article |
Title: | Donor colonic CD103⁺ dendritic cells determine the severity of acute graft-versus-host disease |
Other Titles: | Donor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease |
Author: | Koyama, M. Cheong, M. Markey, K. Gartlan, K. Kuns, R. Locke, K. Lineburg, K. Teal, B. Leveque-El mouttie, L. Bunting, M. Vuckovic, S. Zhang, P. Teng, M. Varelias, A. Tey, S. Wockner, L. Engwerda, C. Smyth, M. Belz, G. McColl, S. et al. |
Citation: | Journal of Experimental Medicine, 2015; 212(8):1303-1321 |
Publisher: | Rockefeller University Press |
Issue Date: | 2015 |
ISSN: | 0022-1007 1540-9538 |
Statement of Responsibility: | 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 |
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. |
Keywords: | Dendritic Cells T-Lymphocytes Advanced Glycosylation End Product-Specific Receptor |
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/). |
DOI: | 10.1084/jem.20150329 |
Published version: | http://dx.doi.org/10.1084/jem.20150329 |
Appears in Collections: | Aurora harvest 3 IPAS publications |
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hdl_99676.pdf | Published version | 5.89 MB | Adobe PDF | View/Open |
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