Paper published in a journal (Scientific congresses and symposiums)
Azacytidine Enhances Regulatory T-Cells In Vivo and Prevents Experimental Xenogeneic Graft-Versus-Host Disease
Ehx, Grégory; Fransolet, Gilles; de Leval, Laurence et al.
2016In Biology of Blood and Marrow Transplantation, 22 (3), p. 393
Peer Reviewed verified by ORBi
 

Files


Full Text
Ehx et al. Abstract ASBMT.docx
Author preprint (14.93 kB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Abstract :
[en] Background. The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Tregs). Objective. We investigated the impact of AZA on xenogeneic graft-versus-host disease (xGVHD) in a humanized murine model of transplantation, and described the impact of the drug on human T cells in vivo. Methods. In order to induce xGVHD, human peripheral blood mononuclear cells (huPBMC) were administered intravenously in NOD-scid IL-2Rγnull (NSG) mice. Results. AZA successfully improved both survival (p<0.0001) and xGVHD scores (p<0.0001). Further, AZA significantly decreased human T-cell proliferation as well as INF-γ and TNF-α serum levels, and reduced the expression of GRANZYME B and PERFORIN 1 by cytotoxic T cells. In addition, AZA administration significantly increased the function, proliferation and frequency of Tregs through demethylation of FOXP3i1 and higher secretion of IL-2 by conventional T cells due to IL2 gene promoter site 1 demethylation. Interestingly, among AZA-treated mice surviving the acute phase of xGVHD, there was an inverse correlation between the presence of Tregs and signs of chronic GVHD. Finally, Tregs harvested from the spleen of AZA-treated mice were suppressive and stable over time since they persisted at high frequency in secondary transplant experiments. Conclusion. These findings emphasize a potential role for AZA as prevention or treatment of GVHD and other autoimmune diseases.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Ehx, Grégory  ;  Université de Liège > GIGA-R : Hématologie
Fransolet, Gilles ;  Université de Liège > GIGA-R : Hématologie
de Leval, Laurence ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
D'Hondt, Stéphanie
Lucas, Sophie
Hannon, Muriel ;  Université de Liège > GIGA-R : Hématologie
Delens, Loïc ;  Université de Liège > GIGA-R : Hématologie
DUBOIS, Sophie ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'hématologie clinique
Drion, Pierre ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R:Méth. expér.des anim. de labo et éth. en expér. anim.
Beguin, Yves  ;  Université de Liège > GIGA-R : Hématologie
Humblet-Baron, Stéphanie
Baron, Frédéric  ;  Université de Liège > GIGA-R : Hématologie
Language :
English
Title :
Azacytidine Enhances Regulatory T-Cells In Vivo and Prevents Experimental Xenogeneic Graft-Versus-Host Disease
Publication date :
March 2016
Event name :
2016 BMT Tandem Meetings
Event organizer :
ASBMT-CIBMTR
Event place :
Honolulu, United States
Event date :
18-22 February 2016
Audience :
International
Journal title :
Biology of Blood and Marrow Transplantation
ISSN :
1083-8791
eISSN :
1523-6536
Publisher :
Elsevier, Netherlands
Volume :
22
Issue :
3
Pages :
393
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 02 June 2016

Statistics


Number of views
85 (18 by ULiège)
Number of downloads
0 (0 by ULiège)

OpenCitations
 
1

Bibliography


Similar publications



Contact ORBi