Donor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease

Koyama, Motoko, Cheong, Melody, Markey, Kate A., Gartlan, Kate H., Kuns, Rachel D., Locke, Kelly R., Lineburg, Katie E., Teal, Bianca E., Leveque-El Mouttie, Lucie, Bunting, Mark D., Vuckovic, Slavica, Zhang, Ping, Teng, Michele W. L., Varelias, Antiopi, Tey, Siok-Keen, Wockner, Leesa F., Engwerda, Christian R., Smyth, Mark J., Belz, Gabrielle T., McColl, Shaun R., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2015) Donor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease. Journal of Experimental Medicine, 212 8: 1303-1321. doi:10.1084/jem.20150329

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Author Koyama, Motoko
Cheong, Melody
Markey, Kate A.
Gartlan, Kate H.
Kuns, Rachel D.
Locke, Kelly R.
Lineburg, Katie E.
Teal, Bianca E.
Leveque-El Mouttie, Lucie
Bunting, Mark D.
Vuckovic, Slavica
Zhang, Ping
Teng, Michele W. L.
Varelias, Antiopi
Tey, Siok-Keen
Wockner, Leesa F.
Engwerda, Christian R.
Smyth, Mark J.
Belz, Gabrielle T.
McColl, Shaun R.
MacDonald, Kelli P. A.
Hill, Geoffrey R.
Title Donor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
1540-9538
Publication date 2015-07-27
Sub-type Article (original research)
DOI 10.1084/jem.20150329
Open Access Status Not Open Access
Volume 212
Issue 8
Start page 1303
End page 1321
Total pages 19
Place of publication New York, NY, United States
Publisher Rockefeller University Press
Collection year 2016
Language eng
Formatted 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.
Keyword Antigen-Presenting Cells
Bone-Marrow-Transplantation
Steady-State
In-Vivo
Gvhd
Differentiation
Macrophages
Alloantigen
Effector
Subset
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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