Donor colonic CD103+ dendritic cells determine the severity of acute graft-versus-host disease
Details
Publication Year 2015-07-27, Volume 212, Issue #8, Page 1303-21
Journal Title
J Exp Med
Publication Type
Journal Article
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.
Publisher
Rockefeller University Press
WEHI Research Division(s)
Molecular Immunology
PubMed ID
26169940
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2015-07-16 08:58:26
Last Modified: 2015-11-19 10:12:09
An error has occurred. This application may no longer respond until reloaded. Reload 🗙