Differential Effects of Gut-Homing Molecules CC Chemokine Receptor 9 and Integrin-β7 during Acute Graft-versus-Host Disease of the Liver.

Abstract

Homing of allogeneic donor T cells to recipient tissue is imperative for the development of acute graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In this study we show that alteration of T cell homing due to integrin-β7 deficiency on T cells or its ligand MAdCAM-1 in BMT recipients contributes to the pathophysiology of experimental GVHD. In contrast, lack of CC chemokine receptor 9 on donor T cells alters tissue homing but does not impact GVHD survival. We further demonstrate that MAdCAM-1 is aberrantly expressed in hepatic murine GVHD as well as in patients with active liver GVHD. However, infiltration of donor T cells in gut but not liver was dependent of MAdCAM-1 expression, indicating, that homing and/or retention of donor T cells rests on divergent molecular pathways depending on the GVHD target tissue.

• Authors: Alina Schreder, Georgios Leandros Moschovakis, Stephan Halle, Jerome Schlue, Chun-Wei Lee, Angela Schippers, Sascha David, Günter Bernhardt, Arnold Ganser, Oliver Pabst, Reinhold Förster, Christian Koenecke
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 21 Issue 12 Pg. 2069-2078 (Dec 2015) ISSN: 1523-6536 [Electronic] United States
• PMID: 26348893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• CC chemokine receptor 9
• Cell Adhesion Molecules
• Integrin beta Chains
• Madcam1 protein, mouse
• Mucoproteins
• Receptors, CCR
• integrin beta7

Topics

• Adult
• Animals
• Bone Marrow Transplantation
• Cell Adhesion Molecules (genetics, immunology)
• Cell Movement
• Child
• Gene Expression
• Graft Survival
• Graft vs Host Disease (genetics, immunology, mortality, pathology)
• Hepatic Insufficiency (immunology, pathology, surgery)
• Humans
• Integrin beta Chains (genetics, immunology)
• Intestines (immunology)
• Liver (immunology)
• Liver Transplantation
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Middle Aged
• Mucoproteins
• Receptors, CCR (deficiency, genetics, immunology)
• Survival Analysis
• T-Lymphocytes (immunology, pathology)
• Transplantation, Homologous
• Whole-Body Irradiation