| First Author | Koyama M | Year | 2015 |
| Journal | J Exp Med | Volume | 212 |
| Issue | 8 | Pages | 1303-21 |
| PubMed ID | 26169940 | Mgi Jnum | J:226438 |
| Mgi Id | MGI:5697261 | Doi | 10.1084/jem.20150329 |
| Citation | Koyama M, et al. (2015) Donor colonic CD103+ dendritic cells determine the severity of acute graft-versus-host disease. J Exp Med 212(8):1303-21 |
| abstractText | 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. |
