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

Ehx, Grégory
Fransolet, Gilles
de Leval, Laurence
D'Hondt, Stéphanie
Lucas, Sophie
Hannon, Muriel
Delens, Loïc
DUBOIS, Sophie
Drion, Pierre
Beguin, Yves
Humblet-Baron, Stéphanie
Baron, Frédéric

Open PDF

Open link

Publication date

March 2016

DOI

10.1016/j.bbmt.2015.11.917

Publisher

Elsevier BV

ISSN

1083-8791

Citation count (estimate)

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 hum...