Gas6 deficiency in recipient mice of allogeneic transplantation alleviates hepatic graft-versus-host disease.

Détails

ID Serval
serval:BIB_923C5E3D1305
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Gas6 deficiency in recipient mice of allogeneic transplantation alleviates hepatic graft-versus-host disease.
Périodique
Blood
Auteur(s)
Burnier L., Saller F., Kadi L., Brisset A.C., Sugamele R., Baudino L., Bono F., Herbert J.M., Carmeliet P., Schapira M., Izui S., Angelillo-Scherrer A.
ISSN
1528-0020[electronic], 0006-4971[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
115
Numéro
16
Pages
3390-3397
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Growth arrest-specific gene 6 (Gas6) is expressed in antigen-presenting cells and endothelial cells (ECs) but not in T cells. When wild-type (WT) or Gas6(-/-) mice received allogeneic non-T cell-depleted bone marrow cells, hepatic graft-versus-host disease (GVHD) was alleviated in Gas6(-/-) recipients regardless of donor genotype, but not in WT recipients. T-cell infiltration was more prominent and diffuse in WT than in Gas6(-/-) recipients' liver. When mice received 0.5 x 10(6) allogeneic T cells with T cell-depleted allogeneic bone marrow, clinical signs indicated that GVHD was less severe in Gas6(-/-) than in WT recipients, as shown by a significant improvement of the survival and reduced liver GVHD. These data demonstrate that donor cells were not involved in the protection mechanism. In addition, lack of Gas6 in antigen-presenting cells did not affect WT or Gas6(-/-) T-cell proliferation. We therefore assessed the response of WT or Gas6(-/-) ECs to tumor necrosis factor-alpha. Lymphocyte transmigration was less extensive through Gas6(-/-) than WT ECs and was not accompanied by increases in adhesion molecule levels. Thus, the lack of Gas6 in ECs impaired donor T-cell transmigration into the liver, providing a rationale for considering Gas6 pathway as a potential nonimmunosuppressive target to minimize GVHD in patients receiving allogeneic hematopoietic stem cell transplantation.
Mots-clé
Animals, Cell Separation, Chemotaxis, Leukocyte/genetics, Chemotaxis, Leukocyte/immunology, Endothelial Cells/metabolism, Flow Cytometry, Graft vs Host Disease/genetics, Graft vs Host Disease/immunology, Hematopoietic Stem Cell Transplantation/adverse effects, Immunohistochemistry, Intercellular Signaling Peptides and Proteins/deficiency, Intercellular Signaling Peptides and Proteins/genetics, Liver/immunology, Liver/pathology, Lymphocyte Activation/immunology, Lymphocyte Culture Test, Mixed, Mice, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes/cytology, T-Lymphocytes/immunology, Transplantation, Homologous
Pubmed
Web of science
Création de la notice
28/06/2010 18:13
Dernière modification de la notice
03/03/2018 19:31
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