Azacytidine Enhances Regulatory T-Cells In Vivo and Prevents Experimental Xenogeneic Graft-Versus-Host Disease

Details

Serval ID
serval:BIB_30ECDE94A727
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Azacytidine Enhances Regulatory T-Cells In Vivo and Prevents Experimental Xenogeneic Graft-Versus-Host Disease
Title of the conference
BMT Tandem Meetings
Author(s)
Ehx G., Fransolet G., De Leval L., D'Hondt S., Lucas S., Hannon M., Delens L., Dubois S., Drion P., Beguin Y., Humblet S., Baron F.
Address
Honolulu, USA, 2016, 18-22 February
ISSN
1083-8791
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
22
Series
Biology of Blood and Marrow Transplantation
Pages
S393-S393
Language
english
Abstract
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.
Keywords
Hematology, Immunology, Transplantation
Web of science
Open Access
Yes
Create date
29/07/2016 8:25
Last modification date
20/08/2019 13:15
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