Differential Effects of Gut-Homing Molecules CC Chemokine Receptor 9 and Integrin-β7 during Acute Graft-versus-Host Disease of the Liver.
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.
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Alina
A
Schreder
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Georgios Leandros
GL
Moschovakis
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Stephan
S
Halle
Institute of Pathology, Hannover Medical School, Hannover, Germany.
Jerome
J
Schlue
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Chun-Wei
CW
Lee
Department of Pediatrics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Angela
A
Schippers
Department of Nephrology, Hannover Medical School, Hannover, Germany.
Sascha
S
David
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Günter
G
Bernhardt
Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation, Hannover Medical School, Hannover, Germany.
Arnold
A
Ganser
Institute of Molecular Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Oliver
O
Pabst
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Reinhold
R
Förster
Institute of Immunology, Hannover Medical School, Hannover, Germany; Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation, Hannover Medical School, Hannover, Germany. Electronic address: koenecke.christian@mh-hannover.de.
Christian
C
Koenecke
D000328:Adult; D000818:Animals; D016026:Bone Marrow Transplantation; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D002465:Cell Movement; D002648:Child; D015870:Gene Expression; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D048550:Hepatic Insufficiency / Q000276:immunology / Q000473:pathology / Q000601:surgery; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D008099:Liver / Q000276:immunology; D016031:Liver Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009088:Mucoproteins; D054388:Receptors, CCR / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
C119309:CC chemokine receptor 9; D015815:Cell Adhesion Molecules; D039641:Integrin beta Chains; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D054388:Receptors, CCR; C091368:integrin beta7
Bone marrow transplantation; GVHD; T cells