Please use this identifier to cite or link to this item: http://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/).
RMID: 0030032072
DOI: 10.1084/jem.20150329
Appears in Collections:IPAS publications

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