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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
Statement of
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 After six months it is available under a Creative Commons License (Attribution–Noncommercial– Share Alike 3.0 Unported license, as described at licenses/by-nc-sa/3.0/).
RMID: 0030032072
DOI: 10.1084/jem.20150329
Appears in Collections:IPAS publications

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